Hyperpolarized Nuclei for NMR Imaging and Spectroscopy - Lunds ...

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The hyperpolarization techniques increase the nuclear polarization by 5 to 6 orders of magnitude as compared with the thermal polarization, with a corresponding rise in signal. Owing to the increased polarization, MRI can be extended to nuclei other than 1 H, thereby permitting the visualization of, e.g., metabolic processes, which were previously inaccessible. However, the signal increase is counteracted by the much lower concentration of the hyperpolarized nuclei — 10 3 to 10 6 times lower than the 1 H concentration, depending on the specific application. Therefore, each application involving hyperpolarized nuclei needs to be evaluated with respect to the anticipated SNR level. The density of protons ( 1 H) is fairly homogeneous within the body and provides little clinically useful information. The ability of conventional MRI to differentiate between various soft tissues and detect pathology is based instead on the inherently different relaxation times (T1, T2, and T2*) of different tissues. Even so, the achievable dynamic range is below 10 (Albert and Balamore 1998). With the administration of contrast agents containing paramagnetic atoms (e.g., Gd 3+ , Mn 2+ ), the relaxation rates (1 T 1 , 1 T 2 ) will increase proportionally with the concentration of the agent. Depending on the imaging sequence used, the reduced relaxation time can result in either an increased or a decreased signal where the agent accumulates, thereby increasing the image contrast. For a detailed description of MR contrast agents, see, e.g., Merbach and Tóth 2001. The mechanism is fundamentally different for hyperpolarized agents: the hyperpolarized nuclei generate the signal themselves rather than moderating the signal from adjacent protons. A better designation for these agents would therefore be “imaging agent” rather than “contrast agent.” Consequently, hyperpolarized MRI (or MRS) has the advantage of completely lacking background signal, either because the nuclei are not naturally present in the body (noble gases) or because the natural abundance signal is negligible ( 13 C). The signal evolution of hyperpolarized nuclei differs from that of thermally polarized nuclei: once the hyperpolarization has vanished, either by T 1 relaxation or by radiofrequency-(RF) induced depolarization, the enhanced signal cannot be regained. This calls for rapid performance of the experiments and a careful design of the imaging sequences. Sequences traditionally used in MRI may perform suboptimally — or may even be useless — and new strategies will be necessary (Zhao and Albert 1998, Durand et al. 2002, Wild et al. 2002a). 2
By using hyperpolarized imaging agents, MRI and MRS can be employed for the investigation of physiological parameters, which until now have been studied using other modalities, e.g., radioisotope imaging, positron emission tomography, computerized tomography (CT), or ultrasonography. Compared with the traditional modalities, MRI may provide increased spatial and temporal resolution without exposure of a subject to ionizing radiation. As examples of possible applications, quantification of physiological parameters of the lung, e.g., ventilation and perfusion, may be mentioned (Cremillieux et al. 1999). 1.1 Aim The aims of this thesis were to investigate the feasibility of using hyperpolarized agents for MRI and MRS applications, to explore adequate pulse sequences and technical procedures, and to demonstrate new methods for the investigation of lung and vascular function based on hyperpolarized MRI/MRS. More specifically, the aims were: • to investigate the possibility of rapid angiography using a hyperpolarized imaging agent and a fast echo planar imaging (EPI) sequence with respect to scan time, spatial resolution, and SNR. • t o de ve l o p a n d in ve s t i g a t e an o p t i m i z e d p ul s e se q ue n c e — t r u e f a s t im a g i n g w i t h s t e a dy - s t a t e p r e c e s si o n ( t r u eF IS P ) — f o r a n - g io g r a p h ic i m a g in g u s i n g a hy pe r po l a r iz e d i m a g in g a g e n t , a n d to demonstrate high-SNR angiograms in live rats by applying the trueFISP sequence to imaging of hyperpolarized 13 C. • to demonstrate a new strategy for a quantitative measurement of regional pulmonary ventilation based on inhalation of hyperpolarized 3 He gas. • to use the 3 He-based method to study gravity-induced ventilation gradients in the rat lung at different postures, and to compare the results with those obtained from established techniques. • to show how the uptake dynamics of hyperpolarized 129 Xe gas, as measured by an MRS-based technique, can be used to calculate the diffusing capacity and pulmonary perfusion in live rats. 3
Page 1: ��
Page 4 and 5: DOKUMENTDATABLAD enl SIS 61 41 21 O
Page 6 and 7: Doctoral Dissertation Department of
Page 9 and 10: Abstract Based on the principle of
Page 11 and 12: Original papers This thesis is base
Page 13 and 14: Table of Contents 1 Introduction .
Page 15: 1 Introduction The phenomenon of nu
Page 19 and 20: vector addition of all the magnetic
Page 21 and 22: illustrates the difference between
Page 23 and 24: pumping process (Colegrove and Fran
Page 25 and 26: thetic effects, and has been used a
Page 27 and 28: 1 T 1,O2 p = ξ O2 [11] where ξ Xe
Page 29 and 30: 1 2 2 −6 ∝ γC γHrτ c. [17] T
Page 31 and 32: and thus breaks down at very low fr
Page 33 and 34: 230 mT, e.g., Tseng et al. 1998, Du
Page 35 and 36: lation-perfusion ratio (V · A/Q ·
Page 37 and 38: after gas inhalation, due to the wa
Page 39 and 40: tion of an NMR signal from a small
Page 41 and 42: larized gas with air took place as
Page 43 and 44: Table 5. Parameters of the imaging
Page 45 and 46: The images were evaluated with resp
Page 47 and 48: partial pressure present within the
Page 49 and 50: 3.8.2 Measurement procedure The spe
Page 51 and 52: 4.2 Vascular imaging of a 13 C-base
Page 53 and 54: gions. In central lung areas, regio
Page 55 and 56: 4.5 Diffusion capacity and perfusio
Page 57 and 58: 5 Discussion In this thesis, three
Page 59 and 60: due to the increased demand on the
Page 61 and 62: 5.3 Hyperpolarized 3 He ventilation
Page 63 and 64: a theoretical T 1 of ∼38 min in t
Page 65 and 66: eath-holding periods during, e.g.,
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6 Conclusions The phantom study in
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8 References ABRAGAM A, GOLDMAN M.
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CHEN XJ, MÖLLER HE, CHAWLA MS, COF
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GIERADA DS, SAAM B, YABLONSKIY D, C
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KAUCZOR HU, HANKE A, VAN BEEK EJ. A
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OLSSON LE, MAGNUSSON P, DENINGER AJ
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TILTON RF, JR., KUNTZ ID, JR. Nucle
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Paper I
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formance of the gradient system, si
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S. MÅNSSON ET AL. Fig. 2. a-h) EPI
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though several technical issues rem
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Hyperpolarized 13 C MR angiography
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Introduction The most widespread te
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of the gradient moments prior to ea
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Methods Polarization procedure The
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secutive trueFISP images were acqui
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also to several other sources such
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low γ of 13 C reduces the sensitiv
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9. Chawla MS, Chen XJ, Möller HE,
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My 1 0.8 0.6 0.4 0.2 0 0 50 100 150
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Signal [a.u] 100 90 80 70 60 50 40
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a b Figure 5. Series of angiograms
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Paper III
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224 Deninger et al. FIG. 1. Sketch
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226 Deninger et al. FIG. 2. Coronal
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228 Deninger et al. FIG. 6. Histogr
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230 Deninger et al. FIG. 9. Monte C
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232 Deninger et al. 5. Gur D, Draye
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3 He MRI-based measurement of posit
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Introduction It is well known that
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3 He imaging All experiments were p
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coefficients b 1 and b 2, respectiv
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Using VI data after subtraction of
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To investigate whether the calculat
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14. Gur D, Drayer BP, Borovetz HS,
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Table 1. Gradient of VI [cm −1 ]
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Cycle 1 Cycle 2 Cycle 3 Cycle 4 2 s
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a Prone Ventilation index c Supine
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a Prone Supine 0 b 1 R 2 Prone Supi
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Paper V
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Abstract The ability to quantify pu
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lation and perfusion information by
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Applying the conditions at the inne
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where L is obtained from Eq. [8]. V
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After tracheal intubation, the anim
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Parametric analysis The fit of the
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in the LPS-treated group is consist
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3. Worsley DF, Palevsky HI, Alavi A
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enin activity in rats chronically e
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V-20 blood without Xe C a V a (t) L
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V-22 Error in estimated diffusion l
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V-24 NMR Ventilator repetition loop
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Figure 7. The peak amplitudes (circ
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