Visualisering av funktionell och morfologisk hjärt-kärl-diagnostik

Speed Dating CMIV Hjärtkärlvisualiseirng och –diagnostik 20101029, B Janerot Sjöberg 

Visualisering av funktionell och morfologisk 

hjärt-kärl-diagnostik 

* 

- ultraljud med kontrastfocus, EIT och PET 

(Birgitta.Janerot@ki.se) 

I. Vävnadseffekter av ultraljud och kontrast 

Frågeställningar 

� Utveckla och etablera en kliniskt applicerbar metod för bestämning av cellulära 

effekter avseende funktion och morfologi 

� Vid vilket pulstryck och mekaniskt index ses kärl- och cellpåverkan 

� Hur optimera pulssekvenser för visualisering och ev. terapi utan att skada 

Teknologier 

� Ekokardiografi (klinisk resp. modifierbar) 

� Simuleringsprogram modifierade för kontrastbubblor 

� Befintlig cellkultur och kontrast (Sonovue®) 

� FDG och gammaspektrometer (Linköping) 

� Inverterad Ljusmikroskopi 

� Kryo-Elektronmikroskopi 

II. EIT för att monitorera hjärtats ejektionsfraktion och volym 


� Fungerar nyutvecklad EIT för hjärtvolym- och ejektionsfraktionsbestämning? 

� Kan vi förbättra elektroder till band eller väst? 

Teknologier 

� Thoracal Electric Impedance Tomography (Enlight, Dixtal Biomedica, Sao Paulo, 

Brazil) Linköping 

� Bildbehandling (Linköping) 

� Ekokardiografi 

1

Speed Dating CMIV Hjärtkärlvisualiseirng och –diagnostik 20101029, B Janerot Sjöberg 

III. Hitta metabolt aktiva instabila plaque med hjälp av PET 

Frågeställning 

� ”Spotty” hjärtupptag på icke-kardiell FDG-PET - tecken till instabil 

kranskärlssjukdom ? 

� Halsupptag carotisplaque? 

Om inte 

� kan vi detektera detta på bättre sätt ? 

Teknologier 

� PET-CT och FDG (Linköping) 

o Retrospektivt vid icke kardiell FDG-PET (Linköping) 

o Kardiell PET/ stilla kärl-PET (carotis?) 

Forskarmedarbetare sökes lokalt! 

Här är vi som arbetar tillsammans idag: 

KI /Karolinska US 

� Birgitta Janerot S (Prof medicinsk tekonologi, Öl klinisk fysiologi och 

nuklearmedicin; Med bild, funktion och teknologi, CLINTEC KI, Alfred Nobels Allé 

10 3 tr, Flemingsberg; birgitta.janerot@ki.se, 070 5093397) 

� Stig Ollmar (impedans) 

� Reidar Winter (ekokardiografi) 

� Ss Marcus Ressner (postdoc ultraljudskontrast & sjukhusfysik) 

STH 

� Hans Hebert m forskargrupp (elektronmikroskopi) 

� Dmitry Grishenkov (utv. ultraljudskontrast) 

� Lars-Åke Brodin m forskargrupp (funktionella bilder) 

CMIV 

� Vetenskapligt råd 

� Jan Engvall (ultraljud, MR, CT) 

� Hans Knutsson m forskargrupp (bildbeh.) 

LiU/LiO (Linköping): 

� Per Ask m forskargrupp (fysiologisk mätteknik) 

� Folke Sjöberg m forskargrupp (microcirk, anestesi, brännskada) 

� Laila Hübbert (kardiologi) 

� Henrik Ahn m forskargrupp (thoraxkirurgi) 

LU: 

� Tomas Jansson (ultraljudsfysik) 

Med flera 

2

Visualisering av funktionell och 

morfologisk hjärt-kärl hjärt kärl- 

diagnostik 

* 

- ultraljud med kontrastfocus 

kontrastfocus, kontrastfocus 

kontrastfocus, , EIT och PET 

Birgitta Janerot Sjöberg, 

Professor Medicinsk 

Medicinsk Teknologi Teknologi + 

+ Öl 

Öl Klinisk fysiologi fysiologi och och Nuklearmedicin 

Nuklearmedicin 

Medicinsk bild bild, , funktion 

funktion och och teknologi teknologi, , CLINTEC, CLINTEC, KI 

KI 

Alfred Nobels Nobels Allé 

Allé 10 10 3 3 tr tr, , Flemingsberg 

Flemingsberg 

Speed Dating CTMH 20101029 

Hjärtkärlvisualisering och -diagnostik 

EIT för för att att monitorera 

monitorera hjärtats 

hjärtats 

ejektionsfraktion och och och volym 

volym 


Teknologier 

�� Fungerar nyutvecklad EIT för �� 

hjärtvolym hjärtvolym- och 

ejektionsfraktionsbestämning 

ejektionsfraktionsbestämning? 

Thoracal Electric 

Impedance Tomography 

(Enlight Enlight, , Dixtal Biomedica, 

�� Kan vi förbättra elektroder till 

band eller väst? 

Sao Paulo Paulo, Brazil) 

�� Bildbehandling 

�� Ekokardiografi 

Forskarmedarbetare 

�� KI /Karolinska US 

– Birgitta Janerot S 

– Stig Ollmar (impedans) 

– Reidar Winter ( (ekokardiografi 

ekokardiografi) 

– Ss Marcus Ressner (postdoc postdoc 

ultraljudskontrast & sjukhusfysik) 

�� STH 

– H Hans Hebert H b t m f forskargrupp k 

(elektronmikroskopi) 

– Dmitry Grishenkov (utv. 

ultraljudskontrast) 

– Lars Lars-Åke Åke Brodin m 

forskargrupp (funktionella bilder) 

�� CMIV : 

– Vetenskapligt råd 

– Jan Engvall 

– Hans Knutsson m 

Jan Engvall (ultraljud, MR, CT) 

forskargrupp (bildbeh bildbeh.) .) 

�� Övr. LiU/LiO LiU/LiO: : 

– Per Ask m forskargrupp 

(fysiologisk mätteknik) 

– Folke Sjöberg m forskargrupp 

(microcirk microcirk, , anestesi, brännskada) 

– Laila Hübbert (kardiologi) kardiologi) 

– Henrik Ahn m forskargrupp 

(thoraxkirurgi) 

�� LU: 

– Tomas Jansson (ultraljudsfysik) 

Sökes samarbetspartners ! 

3 

5 

Vävnadseffekter av ultraljud 

och kontrast 


�� Utveckla och etablera en 

kliniskt applicerbar metod 

för bestämning av cellulära 

effekter avseende funktion 

och morfologi morfologi g 

�� Vid vilket pulstryck och 

mekaniskt index ses kärl- 

och cellpåverkan 

�� Hur optimera pulssekvenser 

för visualisering och ev. 

terapi utan att skada 

Teknologier 

�� Ekokardiograf ( (klinisk klinisk resp. 

modifierbar) 

�� Simuleringsprogram 

modifierade difi d fö för 

kontrastbubblor 

�� Befintlig cellkultur och kontrast 

(Sonovue Sonovue®) ®) 

�� FDG och gammaspektrometer 

�� Inv - Ljusmikroskopi 

�� Kryo Kryo-Elektronmikroskopi 

Elektronmikroskopi 

Hitta metabolt aktiva instabila 

plaque med hjälp av PET 


�� ”Spotty Spotty” ” hjärtupptag på 

icke icke-kardiell kardiell FDG-PET FDG PET - 

tecken till till instabil 

instabil 

kranskärlssjukdom ? 

�� Halsupptag carotisplaque? 

carotisplaque 

Om inte 

�� kan vi detektera detta på 

bättre sätt ? 

Teknologier 

�� PET och FDG 

– Retrospektivt vid icke 

kardiell FDG FDG-PET FDG FDG-PET PET 

– Kardiell PET/ stilla kärl- kärl 

PET (carotis carotis?) ?) 

2 

4 

•1

Automated Analysis and Classification of the Physiological 

Condition of the Carotid Artery in 2D Ultrasound Image Sequences 

Hamed Hamid Muhammed 

School of Technology and Health (STH), Royal Institute of Technology (KTH), 

Alfred Nobels Alle 10, SE-141 52 Huddinge, Sweden 

e-mail: hamed@sth.kth.se 

Tel. +46-8-790 48 55 

The objective of research is to develop automated analysis methods for the classification of 

the physiological condition of the carotid artery in 2D ultrasound image sequences. The 

significance of the new methods is that they are intuitive, automatic, reproducible, and 

significantly reduces the reliance upon subjective measures. 

Developed methods: 

Unsupervised segmentation of vessel walls using both spatial and temporal information. 

Automatic speckle tracking to follow the motion of the vessel walls. 

Extraction and computation of useful parameters to be used for the pattern recognition and 

analysis process. 

Both radial and longitudinal motion is considered. 

Characteristic radial distension curves are measured in the inner surface of the vessel wall. 

Spatio-temporal two-dimensional maps describing the progression of wavy patterns along 

vessel walls are generated. 

Fourier analysis is utilized to obtain easy-to-understand-and-use diagnostic features.

Automated Analysis and Classification 

of the Physiological Condition of the 

Carotid Artery in 2D Ultrasound Image 

Sequences 

Hamed Hamid Muhammed 

hamed@sth.kth.se 

Tel. +46-8-790 48 55 

Segmentation result 

Hamed Hamid Muhammed hamed@sth.kth.se Tel. +46-8-790 48 55 

Carotid artery ultrasound image 


Identification of best ROI 

Hamed Hamid Muhammed hamed@sth.kth.se Tel. +46-8-790 48 55

Radial distension curves 


Young case 

Elderly case 

Spatio-temporal map of a healthy case 


Fourier analysis 


Spatio-temporal map of a pathological case 


Spatio-spectral maps 






CTMH Speed Dating, Oct 29th, 2010 

Finite Element Modeling of the Human Heart 

In our project we apply numerical methods to simulate the blood flow in the heart. Based on the model we 

apply changes on the geometry to gain a better understanding of the effects on the fluid. Our goal is that the 

model might answer clinical hypothesis and we can study diseases and its treatment based on computational 

simulations. An important part of the study is to verify the model against medical data. 

1 Short description of the current model 

The current model consists of the left ventricle 

of the heart (LV). The geometry is based on ultrasound 

measurements of the position of the inner 

wall of the LV at different time points during 

the cardiac cycle. We build a three dimensional 

mesh of tethrahedrons at the initial time 

and use a mesh smoothing algorithm to deform 

the mesh so that it fits the dynamic surface geometry. 

Finally, an adaptive ALE space-time finite 

element solver based on continuous piecewise 

linear elements in space and time together with 

streamline diffusion stabilization is used to simulate 

the blood flow by solving the incompressible 

Navier-Stokes equations. Pressure boundary 

conditions are prescribed to model inflow from 

the mitral valve and outflow through the aortic 

valve. 

2 Joint Activities 

Figure 1: Velocity in the left ventricle 

Finite Element Modeling of the Human Heart is a 

project promoted by the Computational Technology 

Labratory (CTL) at KTH. CTL was created in 2008 

with the aim to unify fundamental research on mathematics and computation with applications of high interest 

in science, industry and biomedicine, motivated and inspired by interaction with industry and society. The core 

of our research is computational mathematical modeling (simulation) with differential equations and adaptive 

finite element methods, with implementation of the computational technology in the open source project FEniCS. 

Our project started in collaboration with a group working at Ume˚a University (Mats Larsson et al.) which 

provided us with the geometry of the heart. We are also in contact with Tino Ebbers who is working with 

medical imaging at LiU. 

Another collaboration is our joint activity in the KTH-founded SimVisInt project where we have begun to build 

a platform with research groups in haptic and visualization. In this way interactive simulations of the heart are 

gained which give feedback on auditory, haptic as well as visual information. 

To secure, develop and make our model applicable the discussions, dialogue, feedbacks and inputs from physicians 

are of high importance. We are in contact with medical researchers and clinical doctors from the Ume˚a 

University and Karolinska Institutet.

Jonas Forsslund, 2010-10-25 

KTH School of Computer Science and 

Communication, Department of Human- 

Computer Interaction 

Contact Information 

The HCI department currently consist of over 40 members, of which 16 is PhD students. The 

head of department is professor Jan Gulliksen, gulliksen@kth.se. The group has formed 

several teams and specialized labs of which three a mentioned here (figure 1). The most related 

persons to the medical, visualization and perceptualization areas are: 

Eva-Lotta Sallnäs Pysander, PhD 

Lead of CSC Haptic Lab, evalotta@csc.kth.se, http://bit.ly/cschapticlab 

Kristina Groth, PhD 

Lead of Interaction Design team, project leader Funki-IS, kicki@csc.kth.se 

Gustav Taxén, PhD 

Lead of Visualization and interaction technology team, gustavt@csc.kth.se 

Jonas Forsslund, MSc 

PhD student perceptualization, member of all three above, part of the Interactive Virtual 

Biomedicine (IVB) project together with Alex Olwal, Evalotta Sallnäs Pysander and collaborators 

from other departments (Johan Hoffman, Jeanette Spüler et al) jofo02@kth.se 

Alex Olwal, PhD 

Member of Visualization team and IVB project alx@kth.se 

Figure 1. The author is working in the Intersection of Interaction design team, Visualization &

interaction technology team and haptic lab, designing haptic enabled visualization applications 

for specific tasks.

jofo02@kth.se 

Perceptualization 

Jonas Forsslund, MSc, jofo02@kth.se 

PhD Student Human-Computer Interaction 

Examples of applications 

jofo02@kth.se 

jofo02@kth.se 

Research area 

• Perceptualization is an emerging research field 

extending visualization to include more senses such as 

hearing and touch. 

• Haptic feedback ”the use of touch in combination with 

motor behaviours to identify objects” objects (Apelle, 1991) 

• Collaboration: common ground & awereness 

Interactive Virtual Biomedicine 

Current status: 

• Feel the heart beat. 

• Try different fequencies. 

Future: 

• Support communication 

and collaboration 

collaboration. 

• More data to perceptualize. 

Requests: 

• What would you dream 

to perceive? 

• What complex 

data can we add? 

• How could team work 

concerning medical data 

be improved? 

2010-10-28 

1

Visualizing gene expression in clinical medicine 

Anders Gabrielsen, MD, DMSc, Dept. of Cardiology and Center for Molecular medicine, CMM L8:03 

Background: 

During the past years we have explored the global gene expression (using gene array technology) 

patterns of atherosclerosis and the vulnerable carotid atherosclerotic plaque; i.e. the plaque with the 

highest risk of developing a thrombosis. We have identified target genes which identifies “high risk” 

patients. 

In a similar way we have identified the important inflammatory molecules and responses to ischemia in 

the heart. 

Now, we want to translate this into clinical information. 

Our main goal is to develop clinical imaging tool(s) to visualize gene expression of target genes in vivo 

based on the target genes already identified. 

We are working with all state-of-the art technologies of molecular biology, and have access to all 

modern imaging tools. We would prefer to develop a MR-based platform. 

Contacts: 

Anders Gabrielsen, MD, DMSc, 

Dept. of Cardiology and Center for Molecular medicine, 

CMM L8:03, 17176 Karolinska Hospital, Stockholm 

Tel. 0709 733 886 

e-mail: anders.gabrielsen@ki.se 

Gabrielle Paulsson Berne, PhD, Ass. Prof. 

CMM L8:03, 17176 Karolinska Hospital, Stockholm 

e-mail: Gabrielle.berne@ki.se 

Ulf Hedin, MD, Prof. 

Dept. of Vascular surgery 

e-mail: Ulf.Hedin@ki.se

Molecular pathophysiology of 

cardiovascular disease. 

Anders Gabrielsen, MD, DMSc. 

Department of Cardiology and 

Center for Molecular Medicine 

CMM L8:03, 

Karolinska Hospital 

17176 Stockholm 

BiKE 

BiKE (Biobank of Karolinska 

Endarterectomies) 

To map, identify and understand the key transcript 

Registration of Clinical Data patterns involved in atherosclerosis we have developed 

Informed 

an in house soft-wear, KI GeneConnect, to 

consent 

computerize the handling of gene-array data from each 

patient to the clinical data base. 

Carotid Plaque Blood 

Clinical Data Array Data 

Gene Array+Morphology+Serum Chemistry+DNA 

Clinical parameters are registered in a separate clinical 

database; symptoms, morphology of plaque (duplex), serum 

analysis (eg inflammatory markers as CRP, fibrinogen, 

cholesterols), risk factors (eg smoking, hypertonic, diabetes), 

ongoing medical treatment, and earlier/ongoing disease. 

Clinical Database 

222 Patients – 

110 Arrays 

Women 

32.3% 

Men 

67.7% 

Symptoms 

Antal pat. 

60 

50 

40 

30 

20 

10 

0 

TIA 

AF 

TIA/AF 

Minor Stroke 

Asymptomatiska 

Okänt 

Other Diseases: 

Diabetes: 22% 

Hypertension: 75% 

Medications: 

Statins: 69% 

Time: Symptom-Surgery 

80 

70 

60 

50 

Antal pat. 

40 

30 

20 

10 

0 

Pågående Mindre än 1 Mellan 1 och Mer än 3 Okänt 

symptom månad 3 månader månader 

KI GeneConnect 

-link clinical and 

array data 

Translating the transcriptome in 

athero-thrombotic athero thrombotic and ischemic heart 

disease: 

Stroke and myocardial infarction 

Cardiovascular Research, Center for Molecular Medicine, 

Vascular surgery and Cardiology Departments 

Karolinska Institute and Karolinska University Hospital 

Present Imaging of vulnerable 

lesions 

• Detection of 

macrophage 

infiltration/inflammati 

on in lesion 

• Ultrasound 

• PET-CT (18FDG) 

2010-10-28 

18 FDG 

1

Vision 

We want to visualize: 

Gene expression (we have targets) 

Inflammation (we have targets) 

Intracellular oxygen status (we know tracers) 

Metabolism (we need key targets) 

In Vivo 

2010-10-28 

2

WIDE INTENSITY RANGE SENSOR 

FOR MEDICAL IMAGING 

Invention 

The present invention relates to medical imaging systems for photon 

sensing and for measuring photon fluxes in a wide intensity range, 

thereby the combinations of detection modalities in one single unit. 

The sensor concept utilizes semiconductor technology, and more 

specifically integrated arrays of avalanche photodiodes (APD), com‐ 

monly denoted silicon photomultipliers (SiPM), which operate in dual‐ 

mode: Current integrating mode is used to measure photon flux in the 

high intensity range, and Photon counting (Geiger) mode is used to 

count individual photons at low to moderate values of intensity. 

Application areas 

Photon sensing is an important component in many medical and tech‐ 

nical applications. In medical imaging a primary range of applications 

involve coupling the sensor to scintillators sensitive to X‐rays and 

gamma rays. Due to the excellent energy/time resolution and wide 

intensity range the primary application areas are: 

1. Combined systems for CT and PET using a single detector array. 

2. CT scanners for both conventional current sensitive readout 

mode as well as photon counting mode (low‐dose) where the 

individual X‐ray photons are detected and characterized with‐ 

out influence of electronic noise on the image quality. 

3. Combined therapeutic and diagnostic imaging for medical ra‐ 

diation therapy. 

Advantages 

Detectors based on the new sensor concept can combine functions 

that today are performed in separate detector systems. The result is 

higher performance at potentially lower cost. More specifically; 

• Higher quality of fused images for PET/CT. 

• Higher image quality at lower patient dose for combined pho‐ 

ton counting and standard charge integrating CT. 

• Reduced production cost for PET/CT systems. 

• Compact systems requiring less hospital space. 

• No need for time and resource demanding calibrations of two 

separate detectors. Simplified calibration procedures. 

• Insensitivity to strong magnetic fields can thereby be used to‐ 

gether with magnetic resonance imaging (MRI) systems. 

• Higher patient throughput. 

20010-10-15 

Application areas 

Medical imaging 

Dosimetry 

Radiography 

Status IPR 

Patents (SWE,EP) granted 

Offer 

Licence contract 

Patent purchase 

Development cooperation 

Contact 

CIREA AB 

www.cirea.se 

Prof. Bo Cederwall 

Department of Physics 

The Royal Institute of 

Technology (KTH) 

S‐106 91 Stockholm, 

Sweden 

Fax: +46 (0)8 55378216 

Tel: +46 (0)8 55378203 

cederwall@nuclear.kth.se



20010-10-15 

History of development 

The detector concept has been developed by Professor Bo Cederwall at the Department of Physics, 

Royal Institute of Technology (KTH), Stockholm, Sweden. Prof. Cederwall is specialized in radiation 

detection utilizing scintillators and semiconductor technology. Today a lab scale prototype detector 

exists with clear proof of concept. A compact prototype detector module is under development. 

Offer 

The offer is a licence contract, purchase of the patent and/or development cooperation. 

IPR 

Priority date April 2, 2007 

Priority number, designated state(s), status SE20070000825 SE Granted 

Further applications , designated state(s), status SE531025(C2) SE Granted 

Further applications , designated state(s), status EP2132541(A1) EP Granted 

Business rationale 

Multimodality imaging in particular combined computed tomography (CT) and positron emission 

tomography (PET) has brought a new perspective into the fields of clinical and preclinical imaging. It 

is now widely recognized that the combination of anatomical structures revealed from CT and the 

functional information from PET provides an enhanced diagnostic tool and also offers an important 

research potential. There is also a strongly increasing interest in photon‐counting CT systems due to 

the higher image contrast and lower radiation doses possible using detectors capable of detecting 

and characterizing individual X‐ray photons. Ideally, a CT detector system should be capable of both 

readout modes, although technical solutions have been lacking up to now. 

The worldwide market size for CT is around 7 billion USD with roughly 40.000 installed systems. The 

largest growth areas are cardiology, which drives the development of yet faster systems to enable 

high quality beating heart imaging, and low‐dose CT, driven by a strong increase of children analyses 

and an increased awareness that the radiation dose acquired by patients during a standard CT ex‐ 

amination involves a non‐negligible risk of inducing cancer. The present invention targets the latter 

area and due to its multimodality, low‐dose photon counting CT operation can be included in a high‐ 

speed CT system. The market size for combined PET/CT is about 1 billion USD and has with wide 

margins passed the market of stand‐alone PET systems. The application area oncology drives the 

development of PET/CT systems with 95 % of all executed analyses and an annual growth rate of 30 

%. The present invention would enable a PET/CT scanner with one common detector system and 

thereby higher imaging performance, but also cost savings; both as an initial investment (lower 

manufacturing cost) and as lower operational costs, primarily due to simplified calibration proce‐ 

dures and a higher patient throughput.



APPENDIX: Technical rationale 

20010-10-15 

The photomultiplier tubes used together with scintillator crystals to detect X‐rays and gamma rays in PET and 

CT scanners, as well as single photon emission computed tomography (SPECT) scanners are in current state‐of‐ 

the‐art systems being replaced by photo detectors based on semiconductor technology; conventional photodi‐ 

odes or avalanche photodiodes (APDs). A major rationale behind this ongoing transition to silicon‐based de‐ 

vices is that they can operate in a strong magnetic field and, thus, provide the technology for combined 

CT/SPECT/PET systems and magnetic resonance imaging (MRI) systems. 

Today, different detector and readout systems are used For CT and PET due to the difference in photon ener‐ 

gies and radiation intensities between these two imaging techniques. For PET, the energy‐ and timing informa‐ 

tion of every photon is measured (photon counting mode). In standard CT applications where the flux of X‐ray 

photons is much higher (on the order of 10 9 photons/mm 2 s), current integration is used with a time constant 

adjusted to provide a readout frequency that matches the rotational motion of the detector gantry. The re‐ 

quirement of two separate detector systems implies more complex, expensive and cumbersome radiation 

detection devices than would be the case if both imaging modalities could be supported by a common detector 

system. In addition, a higher image quality would be achievable due to higher image fusion accuracy. 

Standard CT detectors use scintillators coupled to photodiodes providing an electrical current signal propor‐ 

tional to the intensity of illumination. A drawback of these detectors is their inability to provide energy discri‐ 

minatory data or otherwise count the number and/or measure the energy of photons actually received by a 

given detector element or pixel. On the other hand, current mode is the only practical readout mode at the 

very high X‐ray flux rates used for conventional CT examinations. Development of photon counting CT systems 

is currently in focus and is driven by the the higher image contrast and lower radiation doses possible using 

detectors capable of photon counting and energy discrimination. Ideally, a CT detector system should be capa‐ 

ble of both readout modes, although technical solutions have been lacking up to now. 

The silicon photomultiplier (SiPM) photo sensor technology is a highly promising new development for medical 

imaging systems like CT, PET and SPECT. SiPM‐based scintillation detectors, which exhibit excellent timing and 

energy resolution, are also being developed for other applications of radiation detection. Moreover, SiPMs 

require a minimum of front‐end electronics and can be mass produced at low cost. 

The present detector concept is tailored for SiPMs coupled to scintillator crystals, which can be operated in 

either current integrating or photon counting (Geiger) mode. In applications with high radiation fluxes, such as 

high‐speed X‐ray CT imaging or portal imaging systems, utilization of APDs or SiPMs operated in single‐photon 

counting mode is not possible or inefficient due to saturation effects caused by dead time and pulse pile‐up. 

The maximum count rate per detector element in state‐of‐the‐art single‐photon counting systems is well below 

the mean count rate per unit area required in standard CT imaging. In photon counting mode, such as for PET, 

APDs can practically be used for rates up to about 10 MHz, also limited by the decay time of the scintillator. 

Therefore, common photodiodes that photovoltaically generate a current that is essentially proportional to the 

energy flux of the measured radiation are normally used for such high‐dose rate applications. 

Consequently, for applications requiring a wide dynamic range of photon fluxes, such as a combined CT/PET 

system or a CT‐system operating in both photon counting and current integrating mode, two separate detector 

systems have previously been required; one detector system comprising, e.g., common photodiodes for ena‐ 

bling high‐rate current readout needed for fast CT scanning, and one high gain detector system consisting of, 

for example, APDs for enabling high‐resolution single‐photon readout needed for photon counting CT and for 

PET and SPECT scanning. 

The present invention, via its dual mode operation, is designed to overcome this limitation and thereby enables 

a technological leap to multiple‐modality medical imaging with a single type of radiation detector head. This



20010-10-15 

will improve performance and cost efficiency of such systems. 

Another key application is for imaging in connection with radiation‐based cancer therapy where it is important 

to couple as closely as possible the diagnostic imaging of the patient with the portal imaging that is performed 

on‐line to verify the dose delivery. This invention will enable the design of a single detector system that can 

perform diagnostic CT/PET as well as verifying the dose delivery during a cancer therapy session. This will im‐ 

prove the accuracy, quality and efficiency of the dose delivery and lead to higher protection of healthy tissues 

by reducing uncertainties in patient positioning and by providing the possibility of on‐line corrections to the 

therapeutic beam. 

Technical Details 1) 

The present detector concept consists of integrated APD microstructure arrays, often called silicon photomulti‐ 

pliers (SiPMs) or multi‐pixel photon counters (MPPCs), coupled to scintillator crystals. It can be operated in 

both current integrating and photon counting mode. 

A SiPM consists of hundreds or thousands of microcell Geiger mode APDs per mm 2 and typical sensor areas 

range from a below 1 mm 2 up to tens of mm 2 . The area of each sensor (i.e. pixel size in an imaging system) can 

easily be tailored for the application by the manufacturer. The SiPM's main working regime is in the high‐gain 

Geiger mode where the bias voltage, VB, is set above the breakdown voltage Vbr, where a gain of around 10 5 ‐ 

10 6 can be reached. A single photon is sufficient to excite a cell and the output charge is constant, independent 

on the number of incident photons on the cell. The microcells are connected in parallel and thus the output 

charge is proportional to the number of excited cells, i.e. the number of incoming scintillation photons. This 

property introduces an effectively linear response (Eq. 1) with a relatively wide dynamic range if the average 

number of incident photons is small relative to the number of cells. 

An integrated quenching resistor limits the avalanche and allows each cell that has fired to reset after a time of 

the order of tens of nanoseconds. During this time the pixels are effectively shut down and are insensitive to 

incoming photons. This property would normally make the sensor unsuitable for operation in standard CT ap‐ 

plications where very high X‐ray fluxes are commonly used. In high‐speed CT examinations the X‐ray photon 

flux can easily exceed 10 9 photons/mm 2 , which is orders of magnitude higher than the flux that can be sup‐ 

ported by any photon counting detector system. However, if the bias voltage is lowered below the breakdown 

point, the pixels act as normal APDs, i.e. the device has much lower gain but with no pixel dead time, as a 

trade‐off. By reducing the bias voltage to below the breakdown voltage the dynamic intensity range of the 

sensor is extended by many orders of magnitude, restoring the linear response of the sensor for current mode 

operation (e.g. to be proportional to the X‐ray photon energy flux) and allowing for high‐rate applications such 

as standard CT. 

Typical characteristics of current state‐of‐the art SiPMs include; 

• Photon Detection Efficiency of up to ~80% (and expected to improve as the SiPM technology matures) 

• Sensitive to individual photons (embedded gain ~ 10 6 ‐10 7 ) 

• Requires low reverse voltage ~ 20‐80 V and operates at room temperature



20010-10-15 

A first‐stage detector prototype module has been developed as a proof‐of‐concept for combined PET/CT or a 

CT system that combines photon counting readout for low dose applications with standard current mode rea‐ 

dout. An energy resolution of 12.3% at 662 keV with a 137 Cs source was measured using a LSO scintillator. The 

32 keV K X‐ray line from 137 Ba was resolved above the noise level in this measurement, see Fig. 2. This indicates 

a good potential for photon counting of low‐energy X‐rays which is essential in some CT applications. Timing 

resolution is essential, in particular for time‐of‐flight (TOF) PET and it has been measured with 

a 22 Na source together with a BaF2 detector as a reference, resulting in a value of 1.0 ns (FWHM) for the timing 

resolution at Eγ = 511 keV. Both time and energy resolution is expected to improve with optimized optical 

coupling between the scintillator and SiPM. The inherent time resolution of the SiPM sensor is below 100 ps. 

The current generated in the SiPM is measured in parallel with the pulse mode operation by means of a current 

sensitive amplifier (see Fig. 3). The SiPM hence acts as a current generator, the current being proportional to 

the incoming photon energy flux. This can be done simultaneously with the pulse mode operation. However, 

for certain applications it is desirable to optimize the readout in current integrating mode. Typically this occurs 

for very high signal rates. One example is if the device is used for a (system of) scintillation detector(s) for X‐ 

rays or gamma rays. If the number of incident secondary photons per unit area of the device becomes compa‐ 

rable to the pixel density, significant nonlinearities in the sensor response when it operates in photon counting 

mode will be present. Such saturation effects will affect both the current integrating mode and photon count‐ 

ing operation. For event rates which are large with respect to the single‐pixel recovery time or to the decay 

time of the scintillator saturation effects will occur due to pileup. At such event rates, typically above 1 MHz 

per mm 2 , the photon counting mode operation is no longer efficient. In such cases the bias voltage can be re‐ 

duced to below the breakdown voltage, restoring the linear response of the sensor for current integrating 

mode operation. 

Fig. 1 One of the simplest sensor readout 

schemes is presented. Several other varia‐ 

tions exist. For instance, it may be desir‐ 

able to add a protective RC‐circuit be‐ 

tween the voltage supply and the SiPM. In 

pulse mode, the signals generated by the 

SiPM can be used directly (the SiPM has an 

intrinsic gain of the order of 10 6 – 10 7 ) or 

optionally be amplified before being sent 

on to the pulse processing electronics (not 

shown in the figure). If amplifiers are used, 

only relatively simple, low‐gain (~x10) 

devices are needed. The mean current 

generated by the SiPM is read out simulta‐ 

neously. For event rates which are large 

with respect to the detector time response 

characteristics, like the single‐pixel recov‐ 

ery time or to the decay time of the scintil‐ 

lator, saturation effects will occur due to 

pileup. At high flux rates the sensor can 

therefore be switched seamlessly to pure 

current mode operation by lowering the 

bias voltage below the breakdown value. 

The dynamic intensity range is thereby 

increased by many orders of magnitude.

WIDE INTENSITY RANGE DETECTOR 


2010-08-04 

Fig 2. Energy spectrum of gamma‐ and X‐ 

rays from a radioactive source ( 137 Cs) taken 

with the first‐stage prototype module. 

Fig 3. Correlated current and pulse measure‐ 

ment using a laser diode taken with the first‐ 

stage prototype module. 

1) For further details see: Andreas Persson, Anton Khaplanov , Bo Cederwall and Christian Bohm, 

“A prototype detector module for combined PET/CT or combined photon counting/standard CT based 

on SiPM technology”, to be published in IEEE transactions on Nuclear Science.

Optical sensor with a wide dynamic intensity range 

“wide-range photodiode” 

Invention based on SiPM (MPPC, MPAD) technology 

Bo Cederwall 

The Royal Institute of Technology (KTH) / CIREA AB 

Wide range sensor for combined medical imaging systems 

Solutions to these challenges: Wide range sensor based on SiPM* technology 

- Can be used in a variety of applications that demand detection of individual photons 

or photon fluxes, here as an integral part of scintillation detectors for X-rays and 

gamma rays. 

- The invention enables the sensor to work with good properties (linearity, sensitivity 

etc) in a very wide intensity range. 

- Functions that are performed by separate systems with today’s technology can be 

integrated into one system. 

-Higher performance and precision 

- Simple calibration procedure in pulse mode (sensor is essentially ”digital”) 

- Cost benefits, more compact imaging systems 


The need for radiation sensors in medical imaging with a wide dynamic intensity range 

Integrated PET/CT detectors 

Our sensor concept enables integrated detector systems with common sensors for anatomical and 

functional imaging. 

Today: separate detector systems handle imaging 

Integrated detector system with common sensors 

Combined photon counting mode and standard mode CT 

CIREA AB Wide range sensor for combined medical imaging systems 

* Also called MPPC, MPAD 

� higher imaging accuracy by 

perfect alignment of images 

� lower cost, higher patient throughput 

� reduced space requirements 

� shorter examinations, reduces patient stigma 

Would enable lower patient doses and higher image contrast by registration and characterization of 

individual photons without noise, when this is possible or necessary 

Specialized photon counting CT imaging systems are under strong development but will have special 

applications like for pediatrics or 3D mammography. Such systems saturate under normal conditions. 

A system that can perform both normal and spectral photon counting CT gives a large clinical advantage. 


CIREA AB 

Basis of the Invention: 

Simultaneous/switchable readout of SiPM sensors in current and pulse mode 

Sensor works in pulse mode (spectral photon counting) as a normal photomultiplier 

or APD + amplifier . 

Typical application scintillation detector for PET/SPECT 

or photon counting CT. (Simultaneous current readout possible) 

For high-intensity applications the sensor is tuned to optimise current readout mode 

(as typically for standard photodiodes in e.g. normal CT applications) 

� ”infinite” intensity range 

Dynamic switching between pulse mode and current mode possible 

CIREA AB

Main target applications 

1. Integrated current mode / spectral photon counting CT 

(”simple” conversion of existing CT systems � shortest path to clinical use and 

the lowest investment threshold) 

1. Integrated PET/CT 

2. Combined therapeutic and diagnostic imaging 


PET/CT – future today 

Original picture from Siemens Medical 


PET/CT 

Hybrid of two basic imaging modalities 

CT scanner (high-resolution anatomical images) 

PET scanner (high-quality functional images) 

Computer and software fuses images 

No patient movement between registrations 

“Look into the body and see what happens there (on a molecular level)” 


PET/CT – possible implementation in CT mode 


CIREA AB 

Original picture from Siemens Medical 

CIREA AB

Integrated standard / spectral photon counting CT system 

Counts and characterizes individual X-ray photons 

Can measure the energy of every detected X-ray photon and achieve 

better image contrast sensitivity for a given dose 

Needed for pediatric examinations and 3D mammography where dose is a 

key factor 

System includes high count rate capability of standard CT for conventional 

examinations 

Dynamic switching between modes 


IP – CIREA AB 

“System and method for photon detection”, B. Cederwall /CIREA AB 

Priority date 

April�2,�2007 

Priority number, designated state(s), status SE20070000825 SE Granted 

Further applications , designated state(s), status SE531025 (C2) SE Granted 

Further applications , designated state(s), status EP2132541 (A1) EP Granted 


Integrated Portal – diagnostic (CT/SPECT/PET) imaging for cancer therapy 

Today’s diagnostic imaging is typically performed separate from radiation therapy 

sessions 

This reduces accuray in cancer treatment due to patient movement, anatomical 

changes with time (dose delivery usually via multiple sessions over several 

weeks) 

(Large effort on IMRT and planning, less on this problem) 

Therapeutic imaging yields poor resolution and contrast and requires high-rate 

radiation hard sensors. 

Large potential gain with integrated therapeutic and diagnostic detector system 

Solution: wide-dynamic-range radiation sensor 

� Identical patient – detector alignment 

� High-quality fused anatomical and therapeutic images 

� Lower dose to healthy tissue, higher killing power (lower recurrence rate) 


Where we are 

Proof of concept established 

IP protection in place 

Basic prototype demonstrator near completion 


CIREA AB 

CIREA AB

Vision 

The new sensor concept is applied in the three key application areas: 

Combined current mode / spectral photon counting CT. 

Here only detector heads and software need be replaced in current CT systems – 

the shortest path to clinical use of the technology. 

Integrated PET/CT 

Combined therapeutic/diagnostic imaging system for cancer therapy, largely 

based on PET/CT. 


Background information 


Commercial implementation routes 

We develop detector modules for key applications, in collaboration with systems 

manufacturer. 

We license/ sell IP to systems / component manufacturer, in combination with the 

above. 

We license/ sell IP to systems / component manufacturer 


Silicon Photomultiplier (SiPM) – basic characteristics 


CIREA AB 

Detection efficiency, currently ~25%-40% 

Sensitive to single photons (high intrinsic gain ~10 5 -10 7 ) 

Can measure pulsed/continuous photon fluxes due to many active 

elements (~ 100 – 20000 pixels) 

- emulates function of classic PM tubes 

Operational characteristics: 

– Needs low bias voltage ~20-80 V, 

– Works at room temperature 

– Insensitive to magnetic fields (compatible with MR) 

– Requires a minimum of electronics 

– Dark rate ~ 100 – 500 kHz (single pixels firing) 

Miniatyrized and possible to pack in matrices. 

Low cost (estimated < $10/pce for mass production) 

Recently in production at Pulsar, Hamamatsu Photonics, SensL and others 

CIREA AB

Resistor 

Rn=400 k� 

-20M � 

Al 

Depletion 

Region 

2 �m 

SiPM today-reminder: 

42�m 

20�m 

V bias 

pixel 

Substrate 

h� 

R 50� 

� Pixel size ~20-100�m 


crystal 

photodetector 

PMT 

APD 

SiPM 

� Working point: V Bias = V breakdown + �V ~ 20-80 V 

�V ~ 10-20% above breakdown voltage 

�Each pixel behaves as a Geiger counter with 

Q pixel = �V C pixel with C pixel~50fF � 

Q pixel~150fC=10 6 e 


Electrical inter-pixel cross-talk 

minimized by: 

- decoupling quenching resistor for each pixel 

- boundaries between pixels to decouple them 

� reduction of sensitive area 

and geometrical (packing) efficiency 

Very fast Geiger discharge development < 1 ns 

Pixel recovery time = (Cpixel Rpixel) > ~ 20 ns 

Dynamic range ~ number of pixels � saturation 

SiPM: photon counting detector with “quasi-linear” properties 

preamp 

N photons �PDE 

� � � 

� 

N pixels 

N � � 

� 

firedpixels 

N pixels 1 e 

� 

� 

� 

� 

shaper 

CR-RC 

In Geiger mode the amplitude dynamic range is ~ 10 3 

This is ”perfect” for PET/SPECT (pulse mode) 

A 

D 

C 

• 

• 

• 

SiPM - structure 

Two steps in the development of SiPMs 

� STEP 1: Single Photon Avalanche Diode : Geiger-mode APD (SPAD) � “single pixel photon counter” 

� STEP 2: Integrated Matrix of SPADs with common (parallel) readout: 

Silicon Photomultiplier (SiPM) 

Depletion 

1-2�m 

substrate 

V b 

R 50� 


h� 

50� 

Multipixel Geiger mode 

photodiode with common 

readout. 

Area typically �1-10 mm 2 

Microcell structure on 

common silicon substrate 

“Simple” CMOS technology. 


CIREA AB 

Spectral response with 241Am and 22Na @ 60, 511 and 1274 keV 

Saturation effects due to finite number of pixels 

CIREA AB

Simultaneous pulse and current mode measurement @ 60 keV, 241 Am source 


High-rate saturation effects ct’d 


High-rate saturation effects 


Current measurement with pulsed LED 

The detector “saturates”* when operated in Geiger mode whereas 

the linear response is retained in the sub-Geiger regime. 


CIREA AB 

* Saturation occurs here first due to the current load, at higher frequencies due to the SiPM recovery time 

CIREA AB

Prototype electronics 

• Multipurpose prototype electronics board* 

• Controlled via labview interface. 

• High bandwith current integrating amplifier for high-speed CT. Will handle rapid 

current fluctuations present during a CT scan. Includes 4 photon counting 

discriminators for ”quick and dirty” spectral PC CT. Read out via NI 6212 USB 8ch 

16-bit FADC, NI6602 4ch counter 

• Charge sensitive preamp (full spectral PC CT, PET) 

• Compact mobile prototype unit ”demonstrator” 

* 8-layer board developed in collaboration with ÅF, to be implemented as ASICs for specific applications 


SiPM “response function”, low-level light 

Q 2phe 

Q1phe Q3phe 

P 

Q 4phe 

Q 5phe 

Q 6phe 


Prototypelektronik i samarbete med ÅF system design 


Excellent timing resoluton (e.g. for PET) 

Two SiPM+LYSO crystals in coincidence 

for two gamma’s of 511 KeV (CFD) 

1400 

1200 

1000 

800 

600 

400 

200 

0 

380 400 420 

TDC channel (1 ch=0.1 ns) 

B. ’ Dolgoshein,LIGHT06 

FWHM=0.78 ns 

Laser (CFD) 

Drake, Chen et al., ANL 


FWHM 28ps 

CIREA AB 

CIREA AB

SiPM insensitive to magnetic fields – MR compatible 

SiPM tested in up to 4T 


CIREA AB

Image fusion – hybid imaging (Kenneth Caidahl et al) 

Hybrid imaging means the combination of different imaging techniques to obtain an image with 

special information which can be difficult for the eye to combine correctly when studying one 

technique at a time. This can be achieved in various ways. 

-Combined equipment with fixed positions, internal plane corrections 

-Spatial sensors for positions 

-Image fusion by pattern recognition 

In the recently started EU project 3Micron (coordinating centre KTH, professor Lars-Åke Brodin), we 

aim at developing a multimodal contrast bubble. This means it should be possible to use with 

ultrasound, magnetic resonance imaging (MR), single photon emission tomography (SPECT) and 

positron emission tomography (PET). It will be possible to use such contrast for one technique at a 

time, but the possibility to combine techniques to illustrate the same process, ideally with 

simultaneous otherwise subsequent imaging, is a major advantage. 

The technique to combine SPECT or PET with computed tomography (CT) is now well established. 

Combination of PET and MRI is emerging. The combination of ultrasound with other techniques 

constitutes the greatest challenge since positioning is free and it means external sensors need to be 

used. Also image fusion by means of pattern recognition is possible, and even with external sensors 

this is required. At least one commercial ultrasound company is working in this direction. 

Image fusion is also interesting for experimental laboratory work, in vivo, ex vivo or for cell cultures. 

The recording by different techniques can be compared. Yet another field is the comparison over 

time regarding development or reduction of pathologic processes like cancer or atherosclerosis. Even 

in very close time relationship for evaluation with and without contrast, comparison of the same 

tissue or structure is essential. 

The described problem is thus essential both for experimental work and in the clinical setting, and 

there are a number of interesting applications. 

References 

Kaufmann PA. Cardiac hybrid imaging: state-of-the-art. Ann Nucl Med 2009;23:325-331 

Even-Sapir E, Keidar Z, Bar-Shalom R. Hybrid imaging (SPECT/CT and PET/CT) – improving the 

diagnostic accuracy of functional / metabolic and anatomic imaging. Semin Nucl Med 2009;39:264- 

275 

Matsuo S, Nakajima K, Akhter N, Wakabayashi H, Taki KJ, Okuda K, Kinuya S. Clinical usefulness of 

novel MDCT / SPECT fusion image. Ann Nucl Med 2009; 23:579-86.

Kenneth.Caidahl@ki.se; prof 

Torkel.Brismar@gmail.com; assoc prof 

Björn.Gustafsson@ki.se; post doc 

Anton.Razuvaev@ki.se; post doc 

Åsa.Barrefelt@ki.se; PhD student 

And more 

KI, 3MiCRON 

Clinical Physiology & Radiology 

Collab 

Groups of prof Lars-Åke Brodin, KTH 

Ulf Hedin, Vasc Surg, CMM and more 

Image 

fusion 

Hybrid 

technique 

Courtesy Dianna Bone 

Dept Clin Physiol Karolinska 

Total 

Small

Decision making tools in the diagnosis of pulmonary embolism 

by means of SPECT/CT imaging 

The scintigraphic diagnosis of pulmonary embolism (PE) is based on visual assessment of perfusion 

scintigraphy combined with ventilations scintigraphy according to PIOPED criteria. 

The revised PIOPED criteria include the assessment of severity of perfusion defect in a different lung 

segment. The size of defect categorized as small= 25 but < 75% and large=>75% 

of lung segment evaluated on planar images. Even widely used for many years, planar perfusionventilation 

(V/Q) scintigraphy has well recognized limitations. 

Introduction of Single Photon Emission Tomography (SPECT) overcomes many of these limitations 

through its ability to generate 3-dimentional imaging data. V/Q SPECT has been shown to have a 

greater sensitivity and specificity than planar imaging and a lower non-diagnostic rate. 

The use of SPECT can facilitate advances in V/Q imaging, including the generation of parametric V:Q 

ratio images, coregistration with Computed Tomography(CT) and more accurate quantification of 

regional lung function. 

New generation of hybrid cameras such as SPECT/CT and PET/CT is now available in several 

modern nuclear medicine centres in Europe and Sweden. 

Given the tomographic nature of both SPECT and CT data, fused images can be obtained by using 

data acquired in a single scanning session on such hybrid camera with a greater registration accuracy. 

Such approach may potentially combine the high sensitivity of SPECT with the high specificity of CT. 

Moreover, hybrid SPECT/CT scanners allow each lobe of the lung to be accurately identified on CT 

and mapped back onto the functional data on SPECT, thereby facilitating anatomically accurate 

assessment of individual lobar contribution to lung perfusion. 

Although the main clinical indication for V/Q scintigraphy is in the evaluation of PE, there are other 

indications in with SPECT/CT should have an important role. For patients with lung cancer before 

lung reduction surgery, it is useful to know the relative contribution to total function of the lobe(S) to 

be excised. Planar scanning has been used for this purpose. However, because of the known 

anatomical overlap of the lobes of the lung this approach is inherently inaccurate. 

By now, there is no commercially available soft wear to perform such mapping or quantification. 

Some references: 

Baley DL, Roach PJ, Bailey EA et al. Development of a cost-effective modular SPECT/CT scanner. 

Eur J Nucl Med Mol Imaging 2007; 34:1415-26 

Ketai L, Hartshorne M: Potential uses of SPECT and CT coincidence fusion images of the chest. Clin 

Nucl med 2001; 26: 433-41. 

Jamadar DA, Kazerooni EA, Martinez FJ et al. Semi-quantitative ventilation/perfusion scintigraphy 

and single-photon emission tomography for evaluation of lung volume reduction surgery candidates: 

description and prediction of clinical outcome. Eur J Nucl med 1999; 26: 734-42. 

Freeman LM, Blaufox MD. Pulmonary Embolism. Seminars in Nuclear Medicine 2008, 38 N6. 

Rimma.Axelsson@ki.se

Decision making tools 

in the diagnosis of 

pulmonary embolism 

by means of SPECT/CT imaging 

MD., Ph.D, Associate Professor 

Rimma Axelsson 

Radiology Department,Karolinska Universitetssjukhus,Huddinge 

CLINTEK, KI 

29 Oktober 2010 

Imaging Pulmonary Embolism (PE) 

• Perfusion scintigraphy ( P or Q) since 1964 

evaluating vascular tree and possible 

occlusions. 

• In order to improve methods specificity 

combination with ventilation ( evaluationg 

bronchial tree) scintigraphy (V) since 1970 

• Findings of perfusion defect with preserved 

ventilation in the corresponding area is called 

for VQ mismatch and considered as a sign for 

PE 

• Planar imaging, 8 projections

X-ray exam VQ scan in patient with PE 

Criteria for VQ scan interpretation: 

modified PIOPED 

• Normal - no perfusion defects 

• Very- low probability- Small VQ matches, with a normal chest Xray. 

Non-segmental perfusion defects, including cardiomegaly, enlarged hila 

or aorta 

• Low probability –Large or moderate focal VQ matches involving no 

more than 50% of the combined lung fields, with no corresponding 

radiographic abnormalities. Small VQ mismatches, with a normal chest xray 

• Intermediate probability – difficult to categorize or not described 

as very low, low or high, including cases with a chest X-ray opacity, pleural 

fluid or collapse. Single moderate VQ match or mismatch without 

corresponding radiographic abnormality 

• High probability – 2 or more moderate/large mismatched perfusion 

defects. Prior cardiopulmonary disease probably requires more 

abnormalities(4 or more). Triple match in one lung with one or more 

mismatch in the other 

Definition of perfusion defects 

• Small 25 och 75% of a segment

MDCT-central PE 

Pulmonary 

segments 

• So, the accurate 

interpretation of VQ 

scans is a chllenging 

cognitive task involving 

integration of perfusion 

and ventilation signal 

with the chest X-ray. 

Further developments in diagnosis 

of PE 

• Multi Detector CT (MDCT) for detection of PE since late 

1990-ties 

• Single Photon Emission Tomography 

(SPECT) beginning of 2000-s – 3-dimentional 

imaging data. Comparable or grater sensitivity 

than MDCT for PE,with no contrast-related 

complications such as allergy and nephropathy, 

low radiation dose to the breast,no need for 

sustained breath hold or injection timing to 

acquisition. 

• SPECT/CT- 

Further developments in diagnosis 

of PE 

• Multi Detector CT (MDCT) for detection of PE since late 

1990-ties 

• Single Photon Emission Tomography 

(SPECT) beginning of 2000-s – 3-dimentional 

imaging data. Comparable or grater sensitivity 

than MDCT for PE,with no contrast-related 

complications such as allergy and nephropathy, 

low radiation dose to the breast,no need for 

sustained breath hold or injection timing to 

acquisition. 

• SPECT/CT-

SPECT perfusion transversal reconstruction SPECT perfusion coronal reconstraction 

SPECT: perfusion + ventilation, coronal 

reconstractions 

Patient with PE?

Quantification before surgical removment of a lob 

in patient with lung cancer 

Is it possible to make a soft 

ware for quantification of 

perfusion defects? 

Rimma.Axelsson@ki.se

POLYMER-SHELLED CONTRAST AGENTS FOR ULTRASOUND, 

SPECT AND MRI. 

Dr. Dmitry Grishenkov 

Ultrasound-based imaging technique is probably the most used approach for rapid 

investigation and monitoring of anatomical and physiological conditions of internal 

organs and tissues. 

The ultrasound imaging technique can be greatly improved by the use of contrast agents 

to enhance the signal from the area of interest relative to the background. Typically 

ultrasound contrast agent (UCA) is a suspension of the microbubbles consist of a gas 

core encapsulated within the solid shell. Generally these devices are injected systemically 

and function to enhance the ultrasound echo. The ideal UCA should be manufactured 

from the biocompatible material; be easily injected into the cardiovascular system either 

using bolus or continuous infusion; be stable during the ultrasound examination; do not 

cause any obstruction of the flow; remain within the blood pool or have well-defined 

specific tissue distribution; after destruction the residues should be safely processed and 

removed from the body. Neither material of the shell no encapsulated gas should be 

harmful or toxic for the organism. From the technical point of view UCA should modify 

the acoustic properties of the tissue, for instance by increasing ultrasound backscattered 

efficiency, or introducing harmonic component to the echo, or combination of both. 

The overall objective of the project is to test novel polymer shelled UCAs as a possible 

new generation of multifunctional contrast agents not only for Ultrasound technique but 

also for MRI and SPECT. 

In recent years, the UCA has moved from being just visualization tool to a new 

multifunctional and complex device for drug or gene therapy and targeted imaging. The 

new medical and technological approach of contrast enhanced ultrasound concerns 

“theranostics”, i.e. combination of therapy and diagnostics. Therapeutic systems are not 

any longer stand alone approach against a disease. On the contrary, they tent to integrate 

in to diagnostic techniques such as ultrasound, MRI and CT. With the help of these 

techniques in combination with novel UCAs local and specific drug delivery become 

possible. Within the frame of the project the surface of the polymer microballoon has 

been decorated with the pharmacological agents and the protocol for cavitation mediated 

release of the drug is established. The cutting-edge result of these integrated functions is 

the administration of a much lower drug dosage, avoiding the side effects of 

pharmaceutical overload. 

The latest trend in contrast enhanced sonography is so called molecular imaging, which is 

non-invasive imaging technique to visualize and monitor in real time very fine changes 

on the molecular level. Nowadays, the key modalities for molecular imaging are MRI, 

SPECT and PET. However, increasing interest is shown in introduction of specific 

targeted contrast ultrasound technique to the molecular imaging due to its unique 

features: high temporal resolution, low-cost and wide availability. 

In conclusion, the proposed polymer-shelled gas-core microbubbles can be considered as 

a prospective next generation of contrast agents, which allows not only multimodality 

image enhancement relevant to diagnostics but also localized and specific drug delivery 

for non-invasive therapy.

Polymer-Shelled 

Contrast Agent 

for 

Ultrasound, SPECT and MRI 

Drug delivery 

Echocardiography 

Dr. Dmitry Grishenkov 

Medical Engineering 

School of Technology and Health KTH 

Flemingsberg, Sweden 

Contrast ultrasound 

Molecular imaging 

Oncology 

Thrombosis 

1 

3 

Microbubble 

Type 

Ideal Contrast Agents 

• Manufactured from biocompatible material 

• Injected 

• Stable 

• Do not cause obstruction 

• Remain within the blood pool 

• Processed by the body 

• Modify acoustic or magnetic properties of RoI 

Ultrasound Contrast Agents 

Average Diameter 

(μm) 

1. Local or specific 

drug delivery 

2. Magnetic material 

3. Radioisotope 

Average Shell 

Thickness (μm) 

MB_pH5_RT 4.1 ± 0.7 0.7 ± 0.1 

MB_pH5_Cool 2.7 ± 0.6 0.5 ± 0.1 

MB_pH2_Cool 2.6 ± 0.5 0.5 ± 0.1 

SonoVue ® 2.5 

(polydisperse 1-10 μm) 

≈2.5×10-3 2 

4

3MICRON (Collaborative EU Project) 

Aims: 

1. Enhancement of the imaging techniques 

2. Combined imaging between US, SPECT 

and MRI will be supported by shellmodified 

microbubbles. 

5

Simulation of arterial flows 

with 

Clinical relevance 

Laszlo Fuchs, Mechanics, KTH 

Background: 

Cardio-vascular diseases cause about 50% of mortalities in Western countries. Most of cardiovascular 

events are related to atherosclerosis and associated problems. Arterial lesions are focal in 

character (near branches and bends in larger arteries) and therefore cannot be explained only in 

terms chemical-immunological processes if the blood composition is assumed to be homogenous. 

Our research addresses some basic questions related to pulsatile blood flows in larger arteries and in 

particular in branches. 

Goals: 

The projects are aimed both at basic understanding of the flow itself, the interaction between the 

flow and the blood and the effects of the flow on the arterial walls. Additionally, we apply the basic 

understanding to problems of clinical interest. 

Understanding of the fluid mechanical contribution to atherosclerosis has been a topic of research 

over long time. It is believed that the flow itself only cannot explain the very slow and multifacetted 

process of atherosclerosis. Our hypothesis is the flow affects not only the stresses on the 

walls of the arteries but also the composition of the blood (cells and solvents) locally, whereby the 

process becomes localized. Local blood composition changes also the rheology of the blood which 

results in modification of the flow itself. This impact of this non-linear interaction is unknown. 

Potential clinical applications: 

The forces acting on the walls of the arteries and the physiological response to the temporarily and 

spatially varying stresses may also lead to aneurysm. The flow is also affected by the particular type 

of arterial reconstruction. Understanding these aspects can lead to patient specific arterial (and 

bypass) surgery. Similarly, blood flow in extracorporeal systems (e.g. heart-lung machines, 

hemodialysis) can be improved and/or reducing hazard by utilizing the gained knowledge. 

Methods and models: 

We use computational and experimental tools for studying the flow, mixing and vessel-flow 

interaction in relevant geometries. We are developing models for blood rheology based on the local 

red-blood-cell and macro-molecule concentration. We also develop models for describing the local 

distribution of solvents with different diffusivities (depending on molecule size). The forces acting 

on the walls and the resulting deformation of the vessel is also included in the modelling research. 

The experimental work includes measuring the flow (time-resolved local velocity vector), and local 

concentrations of substances with different molecular diffusivities. All measurements are done 

using non-intrusive methods. We measure the velocity using Laser Doppler Velocimetry (LDV) or 

Particle Image Velocimetry (PIV). These methods are more accurate than ultra-sound based 

technique which is more suitable for optically opaque cases. Concentration of solvents is measured 

simultaneously with the velocity using Laser Induced Fluorescence (LIF) utilizing multiple lasers.

Contact information: 

Prof. Laszlo Fuchs 

Department of Mechanics 

KTH 

Tel: 08-790 7155 

Mobile: 070-5728466 

e-mail: lf@mech.kth.se 

Recent publications: 

1. P. Evegren, J. Revstedt and L. Fuchs -Wall Shear Stress Variations in a 90-degree Bifurcation 

in 3D Pulsating Flows, Medical Engineering & Physics, 32, pp.189–202, 2010. 

2. P. Evegren, J. Revstedt and L. Fuchs - On the secondary flow through bifurcating pipes. Phys. 

Fluids, 22, 103601, doi:10.1063/1.3484266, 2010 

3. P. Evegren, J. Revstedt and L. Fuchs - Pulsating flow and mass transfer in an asymmetric 

system of bifurcations. Submitted to Computers and Fluids.

v/v peak 

Simulation of arterial flows 

with with 

Clinical Clinical relevance relevance 

Laszlo Fuchs 

101029 

Dept. of Mechanics 

KTH 

Arterial flow in a bifurcation 

Generalized geometries 

• Circular cross-section 

• Rigid smooth walls 

1 

0.9 

0.8 

0.7 

0.6 

0.5 

0.4 

0.3 

0.2 

0.1 

Inlet 

0 

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 

t/T 

Outlets 

Boundary conditions 

• Pulsating inlet velocity 

• No slip wall condition 

• Pressure outlet (0 gauge) 

1. Goals 

Outline 

a. Basic understanding of 

i. Atherosclerosis 

ii. Aneurysm � rupture 

iii. Dynamics of blood component distribution 

iv. Blood rheology 

b. Clinical aspects 

i. Stent insertion 

ii. Patient specific reconstruction 

iii. Dialysis 

iv. Hemodilution 

2. Examples 

i. Flow dynamics 

ii. Time- & space-variation of Wall Shear Stress 

iii. Solvent distribution 

Selected Results 

� � 

6 

. 75 

Re �1450 

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areas of negative 

axial WSS.

Experiment 


� �11. 

75 

Re �1450 

Black dots show 

areas of negative 

axial WSS. 


Scalar distribution 

• Distribution affected 

by inlet BC 

Only one region 

Sc=6800 


Axial flow contours 

� � 

separation 

6 

. 75 

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zero contour

Integration of Finite Element Simulations in the clinical work flow of Abdominal Aortic 

Aneurysm patients 

T.Christian Gasser, PhD, KTH Solid Mechanics 

Jesper Swedenborg, MD, PhD, Department of Molecular Medicine and Surgery at KI 

Joy Roy MD, PhD, Department of Molecular Medicine and Surgery at KI 

Martin Auer, PhD, VASCOPS GmbH, Austria 

Vascular biomechanics – Computer simulations of clinical problems 

Interdisciplinary research in the field of biomechanics, with particular emphasize on simulation 

techniques to solve clinically relevant problems. Previous and current work includes: 

o In-vitro experimental investigation of soft biological tissues. 

o Reconstruction of vascular bodies from Computer Tomography Angiography (CT-A) images 

for Finite Element (FE) analysis. 

o Continuum mechanical modeling of the non-linear elastic, the visco-elastic and the elastoplastic 

properties of vascular tissue. 

o Computational Fluid Dynamics (CFD) of blood flow through normal and diseased arteries. 

o Numerical description of non-linear failure mechanics by means of the discontinuous FE 

method and cohesive zone models. 

o Modeling growth of Abdominal Aortic Aneurysms 

Requested additional know-how 

Imaging with emphasize on functional imaging of vascular tissues. 

Research project in the field of biomedical engineering 

o Young Faculty Grant No. 2006-7568. 'Integrated biomechanically based diagnoses of 

Abdominal Aortic Aneurysms' funded by Swedish Research Council, VINNOVA and the 

Swedish Foundation for Strategic Research (since 2007) 

o Project Grant No. 2008-6837. 'Penetration of soft biological tissues' funded by Swedish 

Research Council (since 2008) 

o Collaborative Project 2006-47. 'Fighting Aneurysmal Disease (FAD)' funded by European's 

Seventh Framework Program (since 2008) 

Affiliation and contact information of group members 

T.Christian Gasser, PhD 

Phone: 0046 8 790 7793 Mobile: 0046 73 4301328 

e-mail: tg@hallf.kth.se 

Webpage: www.hallf.kth.se/vascumech 

Affiliation: Lektor (bitr.) at KTH Solid Mechanics 

Jesper Swedenborg, MD, PhD 

Phone: 0046 8 15201 3689 

e-mail: jesper.swedenborg@ki.se 

Webpage: http://www.cmm.ki.se/en/Research/Cardiovascular-and-Metabolic-Diseases/Vascular- 

Surgery/

Affiliation: Professor emeritus at Department of Molecular Medicine and Surgery at KI 

Joy Roy, MD, PhD 

Phone: 0046 8 15201 3689 

e-mail: joy.roy@ki.se 

Webpage: http://www.cmm.ki.se/en/Research/Cardiovascular-and-Metabolic-Diseases/Vascular- 

Surgery/ 

Affiliation: Vascular surgeon at the Department of Molecular Medicine and Surgery at KI 

Martin Auer, PhD 

Phone: 0043 (0) 660 7675296 

e-mail: martin.auer@vascops.com 

Webpage: http://www.vascops.com / 

Affiliation: CTO at VASCOPS GmbH, Vienna, Austria

Integration of Finite Element Simulations in 

the clinical work flow of Abdominal Aortic 

Aneurysm patients 

T.Christian Gasser, PhD, Department of Solid Mechanics at KTH 

Jesper Swedenborg, MD, PhD, Department of Molecular Medicine and Surgery at KI 

Joy Roy, MD, PhD, Department of Molecular Medicine and Surgery at KI 

Martin Auer, PhD, VASCOPS GmbH, Austria 

Speed Dating Workshop, Oct. 29, Stockholm, Sweden 

Model Definition and Development 

Intended use of the model predictions 

Mechanical Testing 

Microscopy 

Material Model 

Comp. Model 

A4clinics 


Image reconstruction 

Patient data 

Introduction and Background 

Biomechanics as part of the clinical decision making 

process 

Clinical Problem Comp. Model Model Prediction Treatment 

A model represents the real object to some degree of completeness. … 

as simple as possible but not simpler! 


Example– Aneurysm rupture risk assessment 

A4clinics (VASCOPS GmbH) 

CT-A Data 

PPatient i DData 


Maximum Diameter 

Peak Wall Rupture 

Risk (PWRR) 

2010-10-28 

1

Example– Aneurysm rupture risk assessment 

Clinical implication of the Peak Wall Rupture Risk (PWRR) 


http://www.hallf.kth.se/vascumech/ 

http://www.vascops.com/ 

Detailed Information 


Tack! 

2010-10-28 

2

Anders Björling 

St. Jude Medical 

175 84 Järfälla 

Office: 08 - 474 4578 

Cell: 0739 - 737 958 

Visualization of the heart’s venous anatomy 

A pacemaker is connected to one to three leads implanted into or in contact with the 

heart. The purpose of the leads is to sense the heart’s electrical activity and to electrically 

stimulate the heart to initiate a contraction. 

Implantation of a traditional pacemaker, having one or two leads, is a simple procedure. 

Implanting leads into the right atrium (RA) and right ventricle (RV) is very fast. It takes 

in the order of a few minutes to cannulate the subclavian vein, slide the leads into the 

heart, position them in the right location and make sure that the sensing and pacing 

capabilities are sufficient. The complete implantation time is in the order of 45 minutes. 

The procedure is performed under local anesthesia and mild sedation. It is conducted in a 

catheterization lab and fluoroscopy is used to visualize the leads and implant tools needed 

to position the leads. 

Biventricular devices, or CRT devices, have an additional lead accessing the left 

ventricle. This lead is implanted transvenously through the coronary sinus and into a 

coronary vein on the outside of the left ventricle, preferably in a left lateral vein. This 

lead is much more complicated to implant than the ones in the RA or RV; in rare cases 

the lead implantation can take up to several hours. Also, in many cases it’s very difficult 

to implant the lead so one has to be satisfied with a non-optimal position. As previously 

mentioned, the implant procedure is performed in the catheterization lab which means 

that the patient and the physician may be subjected to a large amount of X-ray radiation. 

In order to visualize the venous anatomy on the fluoroscopy images a venogram is 

created. This is done by inflating a balloon in the coronary sinus, injecting contrast and 

taking an X-ray image. This is not always easy and several attempts may be needed. The 

contrast agent affects the kidneys and puts an extra stress on these. Many of the patients 

receiving a CRT device have kidney failure or reduced kidney function why this extra 

stress is very serious. 

Also, in about 30% of all patients the therapy does not work. It is not known why it does 

not always work, but it is thought that lead position is a very important factor. It is 

difficult to know beforehand where it is possible to place the lead in a good position. 

Even if a venogram is made and a vein is found in a good position, it is not always 

possible to place the lead there. The vein may be too thin for the lead to enter or the way 

to it may be very tortuous and difficult to access. 

So in summary, being able to answer the following questions positively would be of great 

value: 

• Is it possible, before the operation begins, to identify those patients in whom it is 

not possible to place the lead in a good position due to their difficult venous 

anatomy? 

• Is it possible, at a very early stage of the operation, to identify those veins which 

can not be accessed due to too small size, too tortuous or other? 

• Is it possible, preferably before the operation begins, to create a venogram without 

using a contrast agent?

3 

Visualization of the heart’s 

venous anatomy 

Anders Björling, St. Jude Medical 

Background 

� A biventricular pacemaker stimulates both the right and 

left ventricle of the heart 

� The aim is to synchronize the cardiac contraction, shown 

to improve survival in heart failure (HF) patients 

� The performance of the therapy relies heavily on the 

position of the left lead placed in a coronary vein 

� The implantation of leads is done in a catheterization lab 

using fluoroscopy (X-ray) 

� To visualize the coronary vein anatomy, a contrast agent 

is injected into the bloodstream 

2 

4 

How do you visualize 

the heart’s venous anatomy 

using a 

non-invasive or minimally y invasive method, , 

without using a 

contrast agent affecting renal function? 

Problems and needs 

� It is difficult to obtain a high quality cardiac venogram 

� It is not always possible to know from the venogram if a lead can be 

implanted in a specific vein or not 

� The used X-ray contrast agent affect renal function, often already 

compromised in HF patients 

� Acquiring a high quality venogram and identifying possible lead 

locations before the operation and without the use of contrast would 

lead to: 

� Shorter procedure times 

� Less exposure to X-ray 

� Higher responder rate as patients in whom a lead can not be 

placed in a good position are identified early 

� Less effect on patients’ kidneys 

1

Pre- and per-operative mapping of substrates for atrial fibrillation 

Mats Jensen-Urstad Dept of Cardiology Karolinska Huddinge 

Techniques 

Contact mapping 

After catheterization but before ablation, multielectrode contact-mapping and voltage map of 

the left atrium is done. In practice a multipolar electrode catheter is moved in the left atrium 

along all walls, and data regarding localization and local electrogram is collected on-line to a 

computer for analysis. A 3-dimensional map is created where local electrograms can be studied 

in detail and the amplitude can be presented in the 3-D picture to identify and quantify areas 

with low voltage indicating fibrosis. 

Non-contact mapping 

Electrophysiological registration will be done with non-contact mapping that is a technique 

where a specially designed multiarray balloon catheter is placed in a heart chamber. Over 

3000 local electrograms is simultaneuosly collected with a time resolution of 2 ms which then 

is presented in a 3-D model where regional electrical activity, propagation speed can be 

analysed beat to beat. 

MRI with late enhancement 

MRI scanning is done 15 min following contrast injection using a 3D inversion recovery, 

repiration navigated, ECG gated, gradient echo pulse sequence.

Pre- and per-operative mapping of substrates for atrial fibrillation 

Mats Jensen-Urstad Dept of Cardiology Karolinska Huddinge 

mail: mats.jensen-urstad@karolinska.se 

tel:08-58580000 psök 7433 

mobile: 0706-301006 

Forskargrupp 

Mats Jensen-Urstad, docent, överläkare 

Jonas Schwieler, docent, överläkare 

Frieder Braunschweig, docent, överläkare 

Per Insulander, PhD, överläkare 

Jari Tapanainen, PhD, överläkare 

Bita Sadigh, PhD, bitr överläkare 

Hamid Bastani, doktorand, bitr överläkare 

Nikola Drca, doktorand, bitr överläkare 

Kristjan Gudmundsson, doktorand, specialistläkare 

Rasmus Havmöller, PhD, specialistläkare 

Samtliga vid elektrofysiologiska sektionen, hjärtklinken Karolinska Universitetssjukhuset 

mail: förnamn.efternamn@karolinska.se

Pre- and per-operative 

mapping of substrates for 

atrial fibrillation 

Mats Jensen-Urstad 

Department of Cardiology 

Karolinska Huddinge 

• Catheter ablation with radio frequency or 

cryo as energy source is used to cure both 

paroxysmal and persistent atrial fibrillation 

• With currrent indications need for 3000- 

4000 procedures/year in Sweden 

• Costly ~100000 SKr/procedure 

• Lower short- and longterm success rate 

than for other ablation procedures 

Background 

• Atrial fibrillation (AF) is the most common 

arrhythmia of clinical significans. In the EU 

about 4,5 million people suffers from AF. 

AF gives rise to extreme economical costs 

with a yearly cost of 3000 €/patient, in 

total 13.5 milliards € yearly in the EU. 

How to improve? 

• Patient selection 

• Techniques

Techniques 

• Multipolar contact and non-contact 

mapping of local ECG. Mapping areas with 

low electrical amplitudes 

• MRI with late enhancement 

Contact and non-contact 

mapping

MRI with late enhancement 

• MRI 

• Gadolinium 

• Delayed Enhancement 

• Scar? Fibrosis? Inflammation? 

Marrouche 2009

Posterior-anterior and anterior-posterior view of enhancemnet (green pattern) vs. normal healthy 

tissue (blue) before ablation in patients with lone AF. 

Marrouche 2009 

Utah I was defined as ≤5% LA wall enhancement, Utah II as >5% and ≤20%, 

Utah III as >20% and ≤35%, and Utah IV as >35%. 

297 patienter med PAF el pers FF 

Marrouche et al 2010 

Marrouche 2009

• Can we by preoperative MRI optimize 

treatment? 

• Can we by intraoperative 

electroanatomical mapping optimze the 

ablation procedure? 

• Do MRI and electro-anatomical mapping 

give the same information?

CTMH Speed Dating, Oct 29th, 2010 

Finite Element Modeling of the Human Heart 

In our project we apply numerical methods to simulate the blood flow in the heart. Based on the model we 

apply changes on the geometry to gain a better understanding of the effects on the fluid. Our goal is that the 

model might answer clinical hypothesis and we can study diseases and its treatment based on computational 

simulations. An important part of the study is to verify the model against medical data. 

1 Short description of the current model 

The current model consists of the left ventricle 

of the heart (LV). The geometry is based on ultrasound 

measurements of the position of the inner 

wall of the LV at different time points during 

the cardiac cycle. We build a three dimensional 

mesh of tethrahedrons at the initial time 

and use a mesh smoothing algorithm to deform 

the mesh so that it fits the dynamic surface geometry. 

Finally, an adaptive ALE space-time finite 

element solver based on continuous piecewise 

linear elements in space and time together with 

streamline diffusion stabilization is used to simulate 

the blood flow by solving the incompressible 

Navier-Stokes equations. Pressure boundary 

conditions are prescribed to model inflow from 

the mitral valve and outflow through the aortic 

valve. 

2 Joint Activities 

Figure 1: Velocity in the left ventricle 

Finite Element Modeling of the Human Heart is a 

project promoted by the Computational Technology 

Labratory (CTL) at KTH. CTL was created in 2008 

with the aim to unify fundamental research on mathematics and computation with applications of high interest 

in science, industry and biomedicine, motivated and inspired by interaction with industry and society. The core 

of our research is computational mathematical modeling (simulation) with differential equations and adaptive 

finite element methods, with implementation of the computational technology in the open source project FEniCS. 

Our project started in collaboration with a group working at Ume˚a University (Mats Larsson et al.) which 

provided us with the geometry of the heart. We are also in contact with Tino Ebbers who is working with 

medical imaging at LiU. 

Another collaboration is our joint activity in the KTH-founded SimVisInt project where we have begun to build 

a platform with research groups in haptic and visualization. In this way interactive simulations of the heart are 

gained which give feedback on auditory, haptic as well as visual information. 

To secure, develop and make our model applicable the discussions, dialogue, feedbacks and inputs from physicians 

are of high importance. We are in contact with medical researchers and clinical doctors from the Ume˚a 

University and Karolinska Institutet.

Contact Information: Finite Element Modeling of the Human Heart 

Project Leader 

Johan Hoffman 

Associate Professor in Numerical Analysis 

School of Computer Science and Communication 

Royal Institute of Technology KTH 

Contact: 



SE-10044 Stockholm 

Sweden 

Email:jhoffman@kth.se 

Phone: +46 (0)8 790 7783 

Homepage: http://www.csc.kth.se/∼jhoffman/ 

Project Members 

Johan Jansson 

Researcher in Numerical Analysis 



Contact: 

CSC 

KTH 

100 44 Stockholm 

SWEDEN 

Email:jjan@nada.kth.se 

Phone: +46 (0)8 790 6417 

Homepage: http://www.csc.kth.se/∼jjan/ 

Jeannette Spuhler 

PhD in Numerical Analysis 



Contact: 

KTH Royal Institute of Technology 

Lindstedtsvägen 3, Plan 5 

Numerisk Analys (NA) 

SE-100 44 Stockholm, Sweden 

Email:spuhler@kth.se 

Phone: +46-8-790 62 67 

Homepage: http://www.csc.kth.se/∼spuhler/

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Medical UIs, Augmented Reality & 

Hybrid Interaction Techniques 

Alex Olwal alx@kth.se www.olwal.com 

Human-Computer Interaction, KTH 

INTRODUCTION 

The fundamental idea of Augmented Reality (AR) is to improve 

and enhance our perception of the surroundings, 

through the use of sensing, computing and display systems. 

This makes it possible to augment the physical environment 

with virtual computer graphics. 

UNOBTRUSIVE AR 

The user experience in AR is primarily affected by the display 

type, the system’s sensing capabilities, and the means 

for interaction. The display and sensing techniques determine 

the effectiveness and possible realism, but may at the 

same time have ergonomic and social consequences. 

Unobtrusive AR emphasizes walk-up-and-use scenarios 

with spontaneous interaction and minimal user preparation. 

Unencumbering technology is emphasized, as it 

avoids setups that rely on user-worn equipment, such as 

head-worn displays or motion sensors. 

Unobtrusive AR merges the real and virtual, while preserving 

a clear and direct view of the real, physical environment, 

and avoiding visual modifications to it. It presents 

perspective-correct imagery without user-worn equipment 

or sensors, and supports direct manipulation, while avoiding 

encumbering technologies. 

Figure 1. Interaction and display are distributed and synchronized 

across multiple mobile devices and the large interactive surface. This 

enables collaborations between local and remote users, enabling 

each user to use the device and input controls of their choice. 

HYBRID INTERACTION TECHNIQUES 

As the capabilities of display systems, mobile devices, ubiquitous 

computing and input devices continue to evolve, 

there are many advantages of a heterogenous blend of interaction 

technologies, as shown in Figure 1. Such hybrid 

user interfaces exploit the ability to distribute and combine 

the interactive capabilities of different devices, to provide 

the best possible user experience. Through tracked mobile 

devices, it is, for example, possible to complement interactions 

with a large display, by overcoming its limitations in 

visual output and touch input as shown in Figure 2. 

Numerous input technologies that can be used for remote 

and unobtrusive sensing of user’s interactions are also becoming 

widely available. These are, in particular, wellsuited 

for Spatial AR configurations, where augmentations 

are created with see-through displays or projectors situated 

in the environment. Figure 3 and 4 show the ASTOR system 

and a range of incorporated technology for directmanipulation. 

Figure 2. A tracked handheld display complements interactions with 

a large projection. The handheld provides higher quality and higher 

resolution(11X) focus in its viewport, while the larger screen provides 

the context. [Olwal and Feiner 2009] 

MEDICAL USER INTERFACES 

We are currently witnessing a technological revolution with 

unprecedented connectivity, mobility, distributed computational 

power, ubiquitous sensing, advanced displays, and 

interactivity, which is especially interesting for medical 

user interfaces. We have started to explore the use of our 

techniques to improve efficiency, safety and quality in various 

medical scenarios, including: 

• Examinations (pre-op): for interpretation / analysis 

• Team meetings /collaboration / planning 

• Tele-medicine / mHealth: Remote consulting and teleexpertise 

for rural areas / developing countries 

• Operation / Surgery: Interaction and visualization for 

more efficient use of current medical imaging equipment. 

• Post-op & education: Validate and improve procedures 

and improve training and experience. 

Figure 3. Left) The ASTOR system uses projectors behind a machine 

operator to illuminate a holographic optical element, which is optically 

combined with the view of the machine, as seen through the safety 

glass. Right) The system extracts real-time measurements from the 

industrial machine, which are presented as autostereoscopic 3D graphics. 

Here, the cutting forces (components and resultant) are rendered 

as 3D vectors at the tip of the tool. [Olwal, Gustafsson, Lindfors 2008] 

Figure 4. The ASTOR system was extended with numerous technologies 

to support unobtrusive and hybrid 3D interaction, using a 

depth-sensing camera, a remote eye tracker, a touch-screen overlay 

and mobile touch-screen devices. [Olwal 2008]

Medical User Interfaces 

Advanced interaction techniques for improved 

understanding, collaboration & access to remote expertise 

Alex Olwal, Ph.D. 

olwal.com 

Human-Computer Interaction, KTH 

Medical UIs 

Collaborators 

• Center for Technology in Medicine and Health, KTH / KI / KS 

• Karolinska University Hospital 

• Karolinska Institutet, Medical University 

• Department of Mechatronics, KTH 

Projects 

• 2D X-rays + 3D sensing & visualization 

The Knowledge Foundation 

• FunkIS (HCI + radiology research) 

VINNOVA – The Swedish Governmental Agency for Innovation Systems 

• Improved usability on mobile devices for the elderly & disabled 

Swedish Institute for Assistive Technologies 

Alex Olwal, Ph.D. 

Display Systems 

Sensing 

Interaction Techniques 

2003-2010 KTH Stockholm, Sweden 

2006 Microsoft Research Redmond, WA 

2005 University of California Santa Barbara, CA 

2002-2003 Columbia University New York, NY 

Medical UIs 

• Examinations, pre-op 

• Domain experts � interpretation / analysis 

• Team meetings � collaboration 

• Communication / planning 

• Remote expertise, overcoming distance 

• Rural areas 

• Developing countries 

• Operation 

• Interaction & visualization 

• Post-op & education 

• Validate, improve, educate, … 

• Efficiency � Safety, Quality, Experience, …

Rubbing & Tapping 

Simple gestures for rapid & precise touch-screen interaction 

CHI 2008 [Olwal, Feiner, Heyman] 

Proc. SIGCHI Conference on Human Factors in Computing Systems 

Best paper nominee 

Medical team meetings 

Enhanced communication & interactivity / mobility & remote expertise 

[Olwal, Frykholm, Groth, Moll & Sallnäs] 

On-going collaboration with Karolinska University Hospital & Karolinska Institute 

Spatially aware handhelds 

Enhancing & complementing interaction with large displays 

TEI 2009 [Olwal & Feiner] 

Proc. International Conference on Tangible & Embedded Interaction 

INTERACT 2009 [Olwal] 

Proc. IFIP TC13 Conference on Human-Computer Interaction 

Ericsson Trade Show Events in 2009 / 2010 

Barcelona, Las Vegas, Boston, Galway, Stockholm, Paris, Amsterdam, San Francisco 

Interactive prototyping sessions

Prototypes & studies 

3D tracking & visualization of 2D X-rays 

Improved efficiency & safety in image-guided surgery 

Visual Forum 2010 [Olwal, Ioakeimidou, Nordberg, Holst & Sundblad] 

Augmenting surface interaction 

Collaboration for multiple users, devices & locations 

• Need HybridSurface slide 

TEI 2009 [Olwal & Feiner] 

Proc. International Conference on Tangible & Embedded Interaction 

INTERACT 2009 [Olwal] 

Proc. IFIP TC13 Conference on Human-Computer Interaction 

Ericsson Trade Show Events in 2009 / 2010 

Barcelona, Las Vegas, Boston, Galway, Stockholm, Paris, Amsterdam, San Francisco 

Unencumbered 3D interaction 

Manipulate 3D data using mobile, gestures & touch 

NordiCHI 2008 [Olwal] 

Proc. Nordic Conference on Human Computer Interaction

Looking for new collaborations 

• The research group has experience and interest in 

• user interfaces / human-computer interaction 

• interactive computer graphics (2D / 3D) 

• visualization 

• image processing / analysis 

• interaction techniques / technologies 

(3D input, touch, large displays, mobile, tablet, gesture, …) 

• We have the techniques – and are interested in both applying them to 

medical / health sciences problems and jointly develop new techniques 

• Examples: 

• New & more efficient user interfaces for various tasks 

• New interaction devices to improve/speed up a procedure 

• Automate processes by analyzing / tracking features in images 

• Overlaid computer graphics on anatomy for assistance & guidance 

• … 

• We also supervise a lot of students (individual projects, B.Sc. / M.Sc. Theses, group 

projects) that are interested in problems from the medical domain. 

Acknowledgements 

Organizers 

• CTMH 

Collaborators 

• Karolinska University Hospital 

• Karolinska Institute 

• Center for Medicine, Health and Technology, 

KTH / KI / KS 

• FunkIS (HCI + radiology research) 

• Department of Mechatronics 

• VITA, Linköping University 

• Computer Graphics & UI lab, Columbia 

University 

• ilab, USCB 

• Department of Production Engineering, KTH 

Funding 

• Swedish Research Council 

• Blanceflor Foundation 

• KK foundation 

• Swedish Institute for Assistive Technologies 

• Engineer’s Science Academy / Innovation 

Bridge 

Equipment, donations & funding 

• Ericsson, Nokia, SonyEricsson, Microsoft 

Research, Mitsubishi, Doro, … 

www.olwal.com � videos & more info

Research project – cardiovascular simulation – October 2010 

The research group is currently working actively with many different aspects of 

cardiovascular simulation. The people in Umeå are active in research about cardiac torsion 

movements and are providing echocardiography speckle tracking data to the NADA KTH 

group specialized in numerical analysis dealing with finite element models and rheology. A 

long tradition of simulation research exists in Linköping, now mainly focused on vascular 

arterial simulation. 

Michael Broomé has been working with simulation models used in education for twenty 

years and is now developing a real-time electrical analogy cardiovascular model including 

different aspects of myocardial function, valvular function, cardiac shunts, vascular function, 

oxygen transport and extracorporeal circulation. 

The general research plan is to merge the vast knowledge in circulatory/cardiac physiology 

and state-of-the-art simulation techniques to improve understanding of cardiac physiology 

and to improve technologies for communicating clinical information about cardiac disease 

states. 

More specific goals are: 

To develop a cardiovascular simulation model relevant to analysis of oxygen transport in 

different setups of ECMO (Extra-Corporeal Membrane Oxygenation) 

To develop a cardiovascular simulation model relevant to treatment of pulmonary 

hypertension in different setups of ECMO (Extra-Corporeal Membrane Oxygenation) 

To develop a 3D finite element model of the left ventricle relevant to studies of cardiac 

torsion and flow vortex formation. 

To develop a 3D finite element model of the entire heart with valves and pericardium 

relevant to studies of AV plane movements and cardiac electrophysiological activation 

sequences in normal physiology and pathological states. 

To integrate a 3D finite element model of the heart with the existing real-time electrical 

analogy complete cardiovascular model.

Research group – cardiovascular simulation – October 2010 

Fredrik Bergholm PhD Mathematics 

fredrik.bergholm@sth.kth.se STH KTH Stockholm 

Lars-Åke Brodin MD PhD Clinical Physiology/Cardiology 

lars-ake.brodin@sth.kth.se STH KTH Stockholm 

Michael Broomé MD PhD Cardiac Anesthesiology/Intensive Care 

michael.broome@karolinska.se ECMO Karolinska Stockholm 

broom@kth.se STH KTH Stockholm 

Tino Ebbers MD PhD Clinical Physiology 

tino.ebbers@liu.se LIU Linköping 

Jan Engvall MD PhD Clinical Physiology 

Jan.Engvall@lio.se LIU Linköping 

Jonas Forslund PhD Student Human-Machine Interaction 

jonas.forsslund@gmail.com NADA KTH Stockholm 

Ulf Gustafsson PhD student Clinical Physiology 

ulf.gustafsson@medicin.umu.se NUS Umeå 

Michael Haney MD PhD Anesthesiology 

michael.haney@anestesi.umu.se NUS Umeå 

Johan Hoffmann PhD Numerical analysis 

jhoffman@csc.kth.se NADA KTH Stockholm 

Jonas Johnson PhD Student Engineering 

jonas.johnson@grippingheart.com STH KTH Stockholm 

Johan Jansson PhD Numerical analysis 

jjan@csc.kth.se NADA KTH Stockholm 

Mats G Larson PhD Mathematics 

Mats.G.Larson@math.umu.se Umeå University 

Alex Olwal PhD Human-Machine Interaction 

alx@kth.se NADA KTH Stockholm 

Roman A´Roch PhD Anesthesiology 

Roman.Aroch@vll.se NUS Umeå 

Eva-Lotta Sallnäs PhD Human-Machine Interaction 

evalotta@csc.kth.se NADA KTH Stockholm

Jeannette Hiromi Spühler PhD student Numerical analysis 

spuhler@kth.se NADA KTH Stockholm 

Anders Waldenström MD PhD Cardiology 

anders.waldenstrom@medicin.umu.se NUS Umeå

Cardiovascular simulation 

Speed dating 

Cardiovascular Imaging and Diagnostics 

School of Technology and Health 

29 October 2010 

Hemodynamic simulation 

•Electric analogue 

•Cardiovascular ”Ohms law” ΔP = R · Q 

•Synchronised changes in pressures and flows 

•Only relevant for static laminar flow 

•Capacitive properties 

•Flow Fl bbefore f pressure ( (≈electric l t i loading l di of f a capacitor) it ) 

•Windkessel (elastic arteries) 

•Inductive properties 

•Pressure before flow 

• ≈acceleration inertance 

Michael Broomé MD PhD 

•Simulation, programming and mathematics 1990- 

At home 

•Cardiac anaesthesia and intensive care 1994-2004 

Umeå, Huddinge, Solna 

•Experimental research PhD 2001 

Circulatoryy physiology p y gy and angiotensin g II 

Umeå 

•ECMO 2004- 

Karolinska – Solna 

•Medical Advisor - Research Dept St Jude Medical AB 2006- 

Järfälla 

•Cardiovascular simulation research 2010- 

School of Technology and Health, KTH Flemingsberg 

Pulmonary 

artery 

Right 

ventricle 

Intrathoracic 

space Pericardial 

space 

Large 

veins Right 

atrium 

CorVascSim model 

Large 

arteries 

CorVascSim 2010 

Real-time simulation of: 

• Systolic heart failure 

• Diastolic heart failure 

• Valvular stenosis and regurgitation 

• Shunts (ASD, VSD, PDA) 

• Pericardial effusion and constriction 

• Intrathoracic pressure variations 

• Septal interaction 

• Arrythmias 

• Aortic coarctation 

• Arteriosclerosis 

• Cardiac catheterisation 

• ECMO 

Pulmonary 

veins 

Pulmonary 

Left 

circulation 

atrium 

Left Aortic 

ventriclevalve 

Ascending 

aorta 

Descending 

aorta 

Systemic 

circulation 

2010‐10‐28 

1

2010‐10‐28 

2

Abstract for CTMH, Oct 2010 

Application of ICT for e-Health, examples from Bangladesh 

Dr. Mannan Mridha and Dr. Lars Åke Brodin 

School of Technology and Health, Royal Institute of Technology, KTH 

Alfred Nobels Alle´ 10, 14152 Huddinge, Stockholm, Sweden 

Nazneen Sultana, Grameen Communication, Dhaka, Bangladesh 

Dr. Mohammad Saiful Islam, B.S.M.Medical University, Dhaka, Bangladesh 

Abstract: 

The most people in the developing countries live in the rural areas. They do not have easy and 

affordable access to qualified medical doctors and medical technology. The rural health workers’ 

quality and performance could be improved significantly, provided they get reliable, robust and cost 

effective medical equipment for proper diagnostic purpose and easy and affordable access to 

medical experts for consultations and education on disease prevention. The potential of ICT offers 

exciting opportunities to do so, by providing knowledge and experience in rural health care settings. 

Based on this reasoning, we have been developing suitable environment for mobile telemedicine 

system for application in developing countries like Bangladesh. The health workers from a rural ICT 

centres are now connected to a group of medical experts who are being educated on the importance 

of clean water, proper sanitation, diet habits, physical activity etc. We have been working with the 

development of mobile telemedicine system deploying affordable diagnostic equipment, 

communication platform and relevant health awareness content and video conference system. 

Appropriate platform for medical data acquisition, storage and transmission has been integrated into 

the Telemedicine system. Another strong component of our work is Capacity building, Education and 

Training employing ICT tools for the rural health care providers and general population, taking the 

importance of local contexts and population characteristics into account. The systems are suitable for 

rural health workers to carry from door to door for monitoring and diagnostic purpose, and for follow 

up treatment. The patients receive better, timely and more responsive care. Rural doctors and 

paramedics will benefit from a more satisfying professional experience by avoiding dangerous 

medical mistakes, reduce number of unnecessary referrals and provide facility for continuous 

education, and in the long run will help socio-economic development.

Presentation at the Centre for Technology in Medicine and Health, Stockholm, Oct 29, 2010 

Application of ICT tools for health care development, 

Examples from Bangladesh 

Dr. Mannan Mridha and Dr. Lars Åke Brodin 

School of Technology and Health, Royal Institute of Technology, KTH, 

Alfred Nobels Alle 10, 14152 Huddinge, Stockholm, Sweden 

Mrs. Nazneen Sultana and Mr. Golam Ansari 

Grameen Communication, Dhaka, Bangladesh 

Mr. Sultan Reza 

Grameen Phone, Dhaka, Bangladeesh 

Dr. Mohammad Saiful Islam 

B.S.M.Medical University, Dhaka, Bangladesh 

Why ICT is important? 

� 

� 

� 

Research includes: 

� application ICT tools, methodologies, strategies and 

available and affordable medical technology in 

different contexts for quality diagnosis. 

� address rural health problems, issues, and concerns by 

sharing knowledge and cooperative action. 

� Using ICT tools to effectively communicate what is 

known about the prevention of communicable, and 

noncommunicable diseases 

What distinguishes the poor from the rich is 

not only that they have fewer assets, but also 

that they are largely excluded from the 

creation and the benefits of scientific 

knowledge. 

Dr. A. Salam

According to the World Health Organization, about 

58 million people died in 2005. 

CVDs in the developing countries, 

need to be addressed: 

• Of the 16.7 million deaths from CVDs every year, 

7.2 million are due to ischaemic heart disease, 

5.5 million to cerebrovascular disease, and 

3.9 million to hypertensive , other heart 

conditions. 

• At least 20 million people survive heart attacks and 

strokes every year, 

requiring costly clinical care, 

and pose huge burden on long-term care resources. 

• And some 80% of all CVD deaths worldwide took place 

in developing, low and middle-income countries 

Lab tests: (Temperature, BP, ECG, Hb, 

Glucose, WBC and Albumin in urin, 

Otoscope)

Lectures focus on to reduce CVD like coronary heart disease and stroke risk 

factors diet and physical activity through multiple educational programs. Risks of 

CVD through effects on blood lipids, thrombosis, blood pressure, arterial function, 

arrythogenesis and inflammation are discussed. 

ICT for empowering women: special 

attention is given to women to improve 

nutrition and health conditions 

� 

� 

� 

�

• 

• 

• 

• 

• 

• 

• 

• 

• 

• 

• 

To make the best use of the ICT tools and 

smart medical devices in developing 

countries joint research partnerships 

have to be established

2D and 3D Dynamic Programming for Detection of Moving Boundaries in 

Ultrasound Images of the Carotid Artery 

By 

Tomas Gustavsson and Peter Holdfeldt 

Department of Signals and Systems 

Chalmers University of Technology 

There exist a variety of methods and techniques for automatic boundary detection in 

ultrasound images. Examples are snakes, active shape models, level sets, graph cuts and 

dynamic programming (DP). All of these methods search for the boundary that minimizes a 

pre-defined cost function. Detected boundaries belong to either a local (snakes, ASM and 

level sets) or a global (graph cuts and DP) minimum. 

We have previously reported an optimal DP algorithm for detection of static 2D boundaries. 

From a region of interest in the image, a cost matrix, CM, is created. We use a weighted sum 

of gradients and intensities in each pixel of the region. A horizontal boundary is formed by 

selecting one row from each column in the cost matrix. In order to favor smooth boundaries, a 

smoothness cost, CS, is added. The smoothness cost for including the points pi = (i, yi) and pi- 

) in the boundary is chosen as 

1 = (i - 1, yi-1 

C 

p 

p 

w 

2 

S ( i, 

i−1 

) = S ( i − i−1) 

y 

y 

where wS is a constant. Let M and N be the number of rows and columns of CM. The 

boundary B = { p1, p2, … ,pN } is selected to minimize the cost 

C 

B 

= C 

M 

( p ) + 

1 

N 

∑ 

i= 

2 

( C ( p ) + C ( p , p ) ) 

M 

i 

S 

i 

i−1 

(1) 

, (2) 

where CM(pi) is the cost of point pi. The global minimum of (2) can be found by the wellknow 

dynamic programming (DP) algorithm. In what follows, we extend the algorithm to be 

applicable to dynamic (moving) boundaries. This is done by considering a dynamic boundary 

as a 3D object. Let CBf be the cost of boundary Bf in frame f, and let CSB(Bf, Bf-1) be an interboundary 

smoothness cost, i.e. the additional cost of selecting boundary Bf in frame f and 

boundary Bf-1 in frame f – 1. In short, this cost is related to the likelihood that Bf and Bf-1 are 

the same boundary at different times. For a sequence with F frames the total cost is

AMS (Artery Measurement System) 

Software for Automated Carotid IMT and Plaque Assessment 

2D and 3D Dynamic Programming for Detection of Moving 

Boundaries in Ultrasound Images of the Carotid Artery 

AMS Features 

IMT and Lumen Measurements (mean, median, min, max, sd) 

Simultaneous Near and Far Wall Measurements 

Easy-To-Use Boundary Editing Tool 

Dual Screen for Simultaneous Still Frame and Clip Viewing 

Time-Dynamic Analysis for Distensibility Measurements 

Quantitative Plaque Assessment 

Regulation 21 Part 11 Compliant 

Dynamic Programming – Minimizing a cost function 

Let M and N be the number of rows and columns of C M . The boundary 

B = { p 1 , p 2 , … , p N }is selected to minimize the cost 

C �C 

( p ) � 

B 

M 

1 

N 

� 

i i� 2 

M i S i i�1 

�C( p ) �C 

( p , p ) � 

where C M (p i ) is the cost of point p i . 

2010‐10‐28 

1

. 

Quadratic cost for vertical boundary deviations Total cost for a sequence with F frames 

C 

S ( pi 

, pi�1 

) � wS 

( yi 

� yi�1 

Summary of the proposed 3D-DP method 

Step 0. Compute the cost matrices (same as for 2D‐ 

DP): 

for f = 1...F 

a) Compute CM,f, the cost matrix for frame f. 

end 

Step 1. Find the candidate boundaries: 

for f = 1...F 

a) Use (5) to compute CC,f, the matrix of constrained 

optimizations for frame f. 

b) Fi Find d the th candidate did t boundaries b d i (B (Bf,i) ) of f fframe f 

with the help of (4). 

c) Remove any doubles among the candidate 

boundaries. 

end 

Step 2. Estimate the movements: 

for f = 2...F 

a) Estimate Δyf, the vertical movement between 

frame f ‐ 1 and f (see (7)). 

b) For all candidates Bf‐1,i in frame f ‐ 1, use (6) to 

predict their position in frame f. 

end 

) 

Step 3. Compute the inter‐boundary 

smoothness cost: 

for f = 2...F 

for i= 1...number of candidates in frame 

f 

for j = 1...number of candidates in 

frame f ‐ 1 

a) Compute the error vector, . 

b) Use e and (8) to compute the inter‐boundary 

smoothness cost, CSB(Bf,i, Bf‐1, j). 

end 

end 

end 

Step 4. Detect the sequence: 

Detect the sequence of boundaries by minimizing 

(3) with dynamic programming. 

2 

Results on real data for 2D and 3D-DP 

I2 I7 

data 

set 

3D‐DP 2D‐DP 3D‐DP 2D‐DP 

1 3.91 ± 4.39 ± 1.29 ± 1.44 ± 

4.90 4.65 0.62 0.75 

2 1.36 ± 1.76 ± 2.77 ± 3.28 ± 

0.46 1.31 2.29 2.26 

3 1.10 ± 1.54 ± 1.45 ± 1.81 ± 

0.22 0.72 0.60 0.70 

4 1.45 ± 2.38 ± 2.08 ± 2.74 ± 

0.63 1.32 1.14 1.34 

all 1.95 ± 2.52 ± 1.90 ± 2.32 ± 

2.63 2.66 1.41 1.53 

2010‐10‐28 

2

Circular pulsating structure 

Generalized cylinder 

AMS Main Publications 

Clinical Validation: 

Wendelhag I., Liang Q., Gustavsson T., Wikstrand J., 

A New Automated Computerized Analyzing System Simplifies 

Readings and Reduces the Variability in Ultrasound Measurement of 

Intima-Media d Thickness. h k 

Stroke, 1997;28:2195-2200. 

Technical Description: 

Liang Q., Wendelhag I., Wikstrand J. and Gustavsson T., 

A Multiscale Dynamic Programming Procedure for Boundary 

Detection in Ultrasonic Artery Images. 

IEEE Trans. on Medical Imaging, 2000;19:127-142. 

Results on generalized cylinder 

for 2D and 3D-DP 

SNR Rmse +/‐ SD 3D‐DP Rmse +/‐ SD 2D‐DP 

1.25 3.66 ± 7.12 23.41 ±2.90 

1.00 13.56 ± 14.43 31.20 ±2.21 

0.75 30.68 ± 12.57 35.19 ±0.95 

2010‐10‐28 

3

GrippingHeart 

GrippingHeart is a Swedish based medtech company, with head office at the Karolinska Science Park, 

outside Stockholm. The company is developing software that synchronizes all information from any 

investigation method of the heart and circulatory system into State Diagrams. The State Diagrams are 

easy to interpret and is visualizing the function of the heart and the circulatory system. 

They are easy to communicate and follow up and can be used in discussions with the patient. State 

Diagrams will obtain more accurate and faster diagnosis and can be an effective tool for homecare units 

as well as for patients, to follow up effects of therapies. The software platform is based on discoveries of 

the heart’s pumping and regulating functions which, by mathematical and mechanical interrelationships, 

makes it possible to visualize the functions of the heart in Cardiac State Diagrams (see example below). 

Products 

The software can be implemented into many variable applications: 

• In ultrasound the software can synchronize the collected information into a Cardiac State Diagram, 

enabling faster and more accurate diagnosis. 

• In pacemaker applications, the Cardiac State Diagram can be a valuable tool to both identify the 

appropriate patient and in adjusting and monitoring the pacemaker, enabling a more optimal usage of 

the pacemaker. 

The software and technology platform, covered by a number of patents, are currently in clinical proof-ofconcept 

testing for usage in ultrasound and pacemaker applications. These trials are underway in close 

collaboration with world leading ultrasound and pacemaker specialists in major Scandinavian university 

hospitals. Exploratory testing in other areas such as foetal diagnosis and sports medicine are also 

ongoing. 

Cardiac State Diagrams (examples) 

Business Model 

2010-10-21 

Normal subject Ishemic patient 

In order to make the products available to the international health care system and for the products to be 

integrated into established and available diagnostic and pacemaker equipments, GrippingHeart is seeking 

collaborations with leading device technology companies. In case you are interested in more information 

about the GrippingHeart opportunity, the platform concept or the ultrasound and pacemaker applications, 

you are welcome to contact: 

Thomas Engberg, CEO 

+46 70 517 3829 

thomas.engberg@grippingheart.com 

www.grippingheart.com

2010‐10‐28 

2 

2 

2010‐10‐28 

1 

1 

Speed Dating 2010-10-29 

Thomas Engberg, CEO 

Cardiac State Diagrams 

Visualizing the heart function 

1 

1 

1 1 

1 

3 

3 

7 

2 7 

1 

1 

7 

4 

6 

Normal Ischemic Patient 

1 

1 

Rating 

9 

3 

: Attention 

: Observe 

: Ok 

7 

6 

6 

8 

8 

1 

4 

7 

7 

The Product 

Visualizing the heart function 

� The Cardiac State Diagram is based on 

mechanical interrelationships of the heart’s 

pumping and regulating functions, enabling 

an easy y to interpret p visualization of the 

heart’s entire function 

� The Cardiac State Diagram is generated from 

a software platform that synchronizes all 

information from any investigation method of 

the heart and the circulatory system 

2010‐10‐28 

Development status 

Clinical testing underway with The State Diagram 

� Pilot studies with the State Diagram in patients and healthy 

subjects have shown convincing results 

� This has been achieved in close collaboration with the 

Huddinge university hospital and KTH 

� Clinical proof-of-concept testing underway, in order to 

demonstrate the feasibility and the true customer value 

with the State Diagram 

2010‐10‐28 

2010‐10‐28 

1

1 st & 2 nd patent 

registered 

Gripping 

Heart AB 

founded 

2010‐10‐28 

3 rd & 4 th patent 

registered 

The Company 

Timelines 

5 th patent 

registered 

Clinical Proof-ofconcept 

studies 

initiated 

2008 2009 2010 2011 

State Diagram 

used in 1 st 

patient 

1 st major 

publication of the 

State Diagram in 

Cardiovascular 

Ultrasound 

The development 

of the technical 

platform is ready 

for clinical testing 

Clinical Proof-ofconcept 

studies 

delivered 

Technical development & Pilot phase Clinical phase Commercial phase 

2010‐10‐28 

Team Members 

�Thomas Engberg, CEO / former VP International Marketing AZ 

�Jonas Johnson, M.Sc E.E, Development Director / co-inventor 

�Stig Lundbäck, MD Ph.D., CSO/ inventor and founder 

�Patric Johnson, Software Development 

�Board of Directors 

2010‐10‐28 

2

Visualisering av funktionell och morfologisk hjärt-kärl-diagnostik

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