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Quantitative Tracer Based MRI Perfusion: Potentials and Limitations
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Tracer based MRI perfusion measurements is a clinically useful tool to assess regional distributions of tissue blood flow and volume. The method may be based on any of the three relaxation mechanisms T1, T1 and T2*, the latter denoted DSC-MRI being the most common. The primary aim of this work was to study the feasibility of obtaining quantitative estimates using these methods.

1) Feasibility of DSC-MRI for kidneys using an iron oxide based contrast agent and the influence of secondary relaxation effects on the results, part of a clinical phase II trial: The method proved feasible and the underestimation induced by secondary relaxation can be corrected for by using a double echo sequence.

2) Influence of blood flow rate on risk factors for developing cerebral ischemia during cardio pulmonary bypass, measurements in pig with gadolinium based DSC-MRI: The results indicated an ischemic threshold level at a blood flow rate of approximately 6 ml/kg/min.

3) The ability of gadolinium based DSC-MRI to detect changes in global blood flow, experimental measurements in pig and numerical simulations: The results support that DSC-MRI can discriminate between global flow levels in the same subject given that all other parameters are kept constant. The results also indicate that calculated perfusion values are highly sensitive to the arterial deconvolution procedure.

4) Influence of differences in blood/tissue relaxivity and secondary relaxation for a gadolinium based contrast agent, measurements in pig and numerical simulations: The blood/tissue relaxivity ratio is not unity and the situation is complicated by secondary relaxation effects. Deconvolution regularization appears to partly counteract the overestimation induced by difference in blood/tissue relaxivity for DSC-MRI.

In summary, the fundamental assumption of equal blood and tissue relaxivity is experimentally shown to be invalid and the influence of this discrepancy is substantial. Several factors contribute to measurement errors, a combination of these factors can incidentally lead to additive errors or error cancellation based on a variety of experimental and analysis conditions. Given that the differences in blood/tissue relaxivity cannot readily be accounted for in a clinical setting, absolute perfusion quantification by tracer based MRI remains challenging if not impossible.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. , 67 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 761
Keyword [en]
MRI, Perfusion, Contrast agent, Relaxivity
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Radiology
Identifiers
URN: urn:nbn:se:uu:diva-171901ISBN: 978-91-554-8330-2 (print)OAI: oai:DiVA.org:uu-171901DiVA: diva2:513134
Public defence
2012-05-16, Auditorium Minus, Museum Gustavianum, Akademigatan 3, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2012-04-25 Created: 2012-03-29 Last updated: 2012-08-01Bibliographically approved
List of papers
1. Quantitative renal cortical perfusion in human subjects with magnetic resonance imaging using iron-oxide nanoparticles: influence of T1 shortening
Open this publication in new window or tab >>Quantitative renal cortical perfusion in human subjects with magnetic resonance imaging using iron-oxide nanoparticles: influence of T1 shortening
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2008 (English)In: Acta radiologica (Stockholm, Sweden : 1987), ISSN 1600-0455, Vol. 49, no 8, 955-62 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Using conventional contrast agents, the technique of quantitative perfusion by observing the transport of a bolus with magnetic resonance imaging (MRI) is limited to the brain due to extravascular leakage. PURPOSE: To perform quantitative perfusion measurements in humans with an intravascular contrast agent, and to estimate the influence of the T1 relaxivity of the contrast agent on the first-pass response. MATERIAL AND METHODS: Renal cortical perfusion was measured quantitatively in six patients with unilateral renal artery stenosis using a rapid gradient double-echo sequence in combination with an intravenous bolus injection of NC100150 Injection, an intravascular contrast agent based on iron-oxide nanoparticles. The influence of T1 relaxivity was measured by comparing perfusion results based on single- and double-echo data. RESULTS: The mean values of cortical blood flow, cortical blood volume, and mean transit time in the normal kidneys were measured to 339+/-60 ml/min/100 g, 41+/-8 ml/100 g, and 7.3+/-1.0 s, respectively, based on double-echo data. The corresponding results based on single-echo data, which are not compensated for the T1 relaxivity, were 254+/-47 ml/min/100 g, 27+/-3 ml/100 g, and 6+/-1.2 s, respectively. CONCLUSION: The use of a double-echo sequence enabled elimination of confounding T1 effects and consequent systematic underestimation of the perfusion.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Radiology
Identifiers
urn:nbn:se:uu:diva-103263 (URN)10.1080/02841850802227139 (DOI)000260046200017 ()18615336 (PubMedID)
Available from: 2009-05-18 Created: 2009-05-18 Last updated: 2012-08-01Bibliographically approved
2. Minimal Safe Arterial Blood Flow During Selective Antegrade Cerebral Perfusion at 20° Centigrade
Open this publication in new window or tab >>Minimal Safe Arterial Blood Flow During Selective Antegrade Cerebral Perfusion at 20° Centigrade
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2011 (English)In: Annals of Thoracic Surgery, ISSN 0003-4975, E-ISSN 1552-6259, Vol. 91, no 4, 1198-1205 p.Article in journal (Refereed) Published
Abstract [en]

Background

Selective antegrade cerebral perfusion (SACP) enables surgery on the aortic arch, where cerebral ischemia may cause neurologic sequels. This study aims to identify the minimum arterial flow level to maintain adequate cerebral perfusion during SACP in deep hypothermia in the pig.

Methods

Two groups of pigs were subjected to SACP at 20°C α-stat. In group 1 (n = 6), flow was stepwise adjusted from 8-6-4-2-8 mL · kg−1 · min−1 and in group 2 (n = 5), flow was kept constant at 6 mL · kg−1 · min−1. Magnetic resonance imaging and spectroscopy were performed at each flow level together with hemodynamic monitoring and blood gas analysis. The biochemical marker of cerebral damage protein S100β was measured in peripheral blood.

Results

Decreased mixed venous oxygen saturation and increased lactate in magnetic resonance spectroscopy was seen as a sign of anaerobic metabolism below 6 mL · kg−1 · min−1. No ischemic damage was seen on diffusion-weighted imaging, but the concentrations of S100β were significantly elevated in group 1 compared with group 2 at the end of the experiment (p < 0.05). Perfusion-weighted imaging showed coherence between flow setting and cerebral perfusion, increase of blood volume across time, and regional differences in perfusion during SACP.

Conclusions

The findings suggest an ischemic threshold close to 6 mL · kg−1 · min−1 in the present model. Regional differences in perfusion during SACP may be of pathogenic importance to focal cerebral ischemia.

Keyword
cerebral perfusion
National Category
Physiology
Research subject
Thorax Surgery
Identifiers
urn:nbn:se:uu:diva-147480 (URN)10.1016/j.athoracsur.2010.12.066 (DOI)000288785800057 ()21353198 (PubMedID)
Funder
Swedish Research Council, k2010-64x-08268-23-3
Available from: 2011-02-25 Created: 2011-02-25 Last updated: 2017-12-11Bibliographically approved
3. Sensitivity of dynamic susceptibility contrast MRI to change in global flow rate
Open this publication in new window or tab >>Sensitivity of dynamic susceptibility contrast MRI to change in global flow rate
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(English)Manuscript (preprint) (Other academic)
Keyword
DSC-MRI, dynamic susceptibility contrast, MRI, perfusion
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Radiology
Identifiers
urn:nbn:se:uu:diva-170530 (URN)
Available from: 2012-03-28 Created: 2012-03-12 Last updated: 2015-06-11
4. Influence of blood/tissue differences in contrast agent relaxivity on tracer based MR perfusion measurements
Open this publication in new window or tab >>Influence of blood/tissue differences in contrast agent relaxivity on tracer based MR perfusion measurements
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2015 (English)In: Magnetic Resonance Materials in Physics, Biology and Medicine, ISSN 0968-5243, E-ISSN 1352-8661, Vol. 28, no 2, 135-147 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE:

Perfusion assessment by monitoring the transport of a tracer bolus depends critically on conversion of signal intensity into tracer concentration. Two main assumptions are generally applied for this conversion; (1) contrast agent relaxivity is identical in blood and tissue, (2) change in signal intensity depends only on the primary relaxation effect. The purpose of the study was to assess the validity and influence of these assumptions.

MATERIALS AND METHODS:

Blood and cerebral tissue relaxivities r1, r2, and r2* for gadodiamide were measured in four pigs at 1.5 T. Gadolinium concentration was determined by inductively coupled plasma atomic emission spectroscopy. Influence of the relaxivities, secondary relaxation effects and choice of singular value decomposition (SVD) regularization threshold was studied by simulations.

RESULTS:

In vivo relaxivities relative to blood concentration [in s-1 mM-1 for blood, gray matter (GM), white matter (WM)] were for r1 (2.614 ± 1.061, 0.010 ± 0.001, 0.004 ± 0.002), r2 (5.088 ± 0.952, 0.091 ± 0.008, 0.059 ± 0.014), and r2* (13.292 ± 3.928, 1.696 ± 0.157, 0.910 ± 0.139). Although substantial, by a nonparametric test for paired samples, the differences were not statistically significant. The GM to WM blood volume ratio was estimated to 2.6 ± 0.9 by r1, 1.6 ± 0.3 by r2, and 1.9 ± 0.2 by r2*. Secondary relaxation was found to reduce the tissue blood flow, as did the SVD regularization threshold.

CONCLUSION:

Contrast agent relaxivity is not identical in blood and tissue leading to substantial errors. Further errors are introduced by secondary relaxation effects and the SVD regularization.

Keyword
MRI, relaxivity, contrast agent, perfusion
National Category
Radiology, Nuclear Medicine and Medical Imaging Analytical Chemistry
Research subject
Radiology; Medical Radiophysics
Identifiers
urn:nbn:se:uu:diva-170528 (URN)10.1007/s10334-014-0452-5 (DOI)000352149200004 ()
Available from: 2012-03-28 Created: 2012-03-12 Last updated: 2017-12-07Bibliographically approved

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