Publications by authors named "Phillip Zhe Sun"

81 Publications

Quasi-steady-state chemical exchange saturation transfer (QUASS CEST) MRI analysis enables T normalized CEST quantification - Insight into T contribution to CEST measurement.

Authors:
Phillip Zhe Sun

J Magn Reson 2021 Aug 8;329:107022. Epub 2021 Jun 8.

Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States; Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta GA, United States. Electronic address:

Chemical exchange saturation transfer (CEST) MRI depends not only on the labile proton concentration and exchange rate but also on relaxation rates, particularly T relaxation time. However, T normalization has shown to be not straightforward under non-steady-state conditions and in the presence of radiofrequency spillover effect. Our study aimed to test if the combined use of the new quasi-steady-state (QUASS) analysis and inverse CEST calculation facilitates T normalization for improved CEST quantification. The CEST signal was simulated with Bloch-McConnell equations, and the apparent CEST, QUASS CEST, and the inverse CEST effects were calculated. T-normalized CEST effects were tested for their specificity to the underlying CEST system (i.e., labile proton ratio and exchange rate). CEST experiments were performed from a 9-vial phantom of independently varied concentrations of creatine (20, 40, and 60 mM) and manganese chloride (20, 30, and 40 µM) under a range of RF saturation amplitudes (0.5-4 µT) and durations (1-4 s). The simulation showed that while T normalization of the apparent CEST effect was subject to noticeable T contamination, the T-normalized inverse QUASS CEST effect had little T dependence. The experimental data were analyzed using a multiple linear regression model, showing that T-normalized inverse QUASS analysis significantly depended on creatine concentration and saturation power (P < 0.05), not on manganese chloride concentration and saturation duration, advantageous over other CEST indices. The QUASS CEST algorithm reconstructs the steady-state CEST effect, enabling T-normalized inverse CEST effect calculation for improved quantification of the underlying CEST system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmr.2021.107022DOI Listing
August 2021

Pulseq-CEST: Towards multi-site multi-vendor compatibility and reproducibility of CEST experiments using an open-source sequence standard.

Magn Reson Med 2021 Oct 7;86(4):1845-1858. Epub 2021 May 7.

Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tuebingen, Germany.

Purpose: As the field of CEST grows, various novel preparation periods using different parameters are being introduced. At the same time, large, multisite clinical studies require clearly defined protocols, especially across different vendors. Here, we propose a CEST definition standard using the open Pulseq format for a shareable, simple, and exact definition of CEST protocols.

Methods: We present the benefits of such a standard in three ways: (1) an open database on GitHub, where fully defined, human-readable CEST protocols can be shared; (2) an open-source Bloch-McConnell simulation to test and optimize CEST preparation periods in silico; and (3) a hybrid MR sequence that plays out the CEST preparation period and can be combined with any existing readout module.

Results: The exact definition of the CEST preparation period, in combination with the flexible simulation, leads to a good match between simulations and measurements. The standard allowed finding consensus on three amide proton transfer-weighted protocols that could be compared in healthy subjects and a tumor patient. In addition, we could show coherent multisite results for a sophisticated CEST method, highlighting the benefits regarding protocol sharing and reproducibility.

Conclusion: With Pulseq-CEST, we provide a straightforward approach to standardize, share, simulate, and measure different CEST preparation schemes, which are inherently completely defined.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mrm.28825DOI Listing
October 2021

Quasi-steady-state CEST (QUASS CEST) solution improves the accuracy of CEST quantification: QUASS CEST MRI-based omega plot analysis.

Authors:
Phillip Zhe Sun

Magn Reson Med 2021 08 10;86(2):765-776. Epub 2021 Mar 10.

Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.

Purpose: CEST MRI omega plot quantifies the labile proton fraction ratio (f ) and exchange rate (k ), yet it assumes long RF saturation time (Ts) and relaxation delay (Td). Our study aimed to test if a quasi-steady-state (QUASS) CEST analysis that accounts for the effect of finite Ts and Td could improve the accuracy of CEST MRI quantification.

Methods: We modeled the MRI signal evolution using a typical CEST EPI sequence. The signal relaxes toward its thermal equilibrium following the bulk water relaxation rate during Td, and then toward its CEST steady state following the spin-lock relaxation rate during Ts from which the QUASS CEST effect is derived. Both f and k were solved from simulated conventional apparent CEST and QUASS CEST MRI. We also performed MRI experiments from a Cr-gel phantom under serially varied Ts and Td times from 1.5 to 7.5 s.

Results: Simulation showed that, although k could be slightly overestimated (3%-15%) for the range of Ts and Td, f could be substantially underestimated by as much as 67%. In contrast, the QUASS solution provided accurate k and f determination within 2%. The CEST MRI experiments confirmed that the QUASS solution enabled robust quantification of k and f , superior over the omega plot analysis based on the conventional apparent CEST MRI measurements.

Conclusions: The QUASS CEST MRI algorithm corrects the effect of finite Ts and Td times on CEST measurements, thereby allowing robust and accurate CEST quantification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mrm.28744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076066PMC
August 2021

Preliminary demonstration of in vivo quasi-steady-state CEST postprocessing-Correction of saturation time and relaxation delay for robust quantification of tumor MT and APT effects.

Magn Reson Med 2021 08 15;86(2):943-953. Epub 2021 Mar 15.

Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China.

Purpose: Chemical exchange saturation transfer (CEST) MRI is versatile for measuring the dilute labile protons and microenvironment properties. However, the use of insufficiently long RF saturation duration (Ts) and relaxation delay (Td) may underestimate the CEST measurement. This study proposed a quasi-steady-state (QUASS) CEST analysis for robust CEST quantification.

Methods: The CEST signal evolution was modeled as a function of the longitudinal relaxation rate during Td and spin-lock relaxation rate during Ts, from which the QUASS-CEST effect is derived. Numerical simulation and in vivo rat glioma MRI experiments were conducted at 11.7 T to compare the apparent and QUASS-CEST results obtained under different Ts/Td of 2 seconds/2 seconds and 4 seconds/4 seconds. Magnetization transfer and amide proton transfer effects were resolved using a multipool Lorentzian fitting and evaluated in contralateral normal tissue and tumor regions.

Results: The simulation showed the dependence of the apparent CEST effect on Ts and Td, and such reliance was mitigated with the QUASS algorithm. Animal experiment results showed that the apparent magnetization transfer and amide proton transfer effects and their contrast between contralateral normal tissue and tumor regions increased substantially with Ts and Td. In comparison, the QUASS magnetization transfer and amide proton transfer effects and their difference between contralateral normal tissue and tumor exhibited little dependence on Ts and Td. In addition, the apparent magnetization transfer and amide proton transfer were significantly smaller than the corresponding QUASS indices (P < .05).

Conclusion: The QUASS-CEST algorithm enables robust CEST quantification and offers a straightforward approach to standardize CEST experiments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mrm.28764DOI Listing
August 2021

Alkaline brain pH shift in rodent lithium-pilocarpine model of epilepsy with chronic seizures.

Brain Res 2021 May 5;1758:147345. Epub 2021 Feb 5.

Harvard Medical School, Boston, MA, 02115, USA; Division of Newborn Medicine, Dept. Pediatrics, Boston Children's Hospital, Boston, MA, 02115, USA. Electronic address:

Brain pH is thought to be important in epilepsy. The regulation of brain pH is, however, still poorly understood in animal models of chronic seizures (SZ) as well as in patients with intractable epilepsy. We used chemical exchange saturation transfer (CEST) MRI to noninvasively determine if the pH is alkaline shifted in a rodent model of the mesial temporal lobe (MTL) epilepsy with chronic SZ. Taking advantage of its high spatial resolution, we determined the pH values in specific brain regions believed to be important in this model produced by lithium-pilocarpine injection. All animals developed status epilepticus within 90 min after the lithium-pilocarpine administration, but one animal died within 24 hrs. All the surviving animals developed chronic SZ during the first 2 months. After SZ developed, brain pH was determined in the pilocarpine and control groups (n = 8 each). Epileptiform activity was documented in six pilocarpine rats with scalp EEG. The brain pH was estimated using two methods based on magnetization transfer asymmetry and amide proton transfer ratio. The pH was alkaline shifted in the pilocarpine rats (one outlier excluded) compared to the controls in the hippocampus (7.29 vs 7.17, t-test, p < 0.03) and the piriform cortex (7.34 vs. 7.06, p < 0.005), marginally more alkaline in the thalamus (7.13 vs. 7.01, p < 0.05), but not in the cerebral cortex (7.18 vs. 7.08, p > 0.05). Normalizing the brain pH may lead to an effective non-surgical method for treating intractable epilepsy as it is known that SZ can be eliminated by lowering the pH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brainres.2021.147345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987840PMC
May 2021

Brain pH Imaging and its Applications.

Neuroscience 2021 Jan 23. Epub 2021 Jan 23.

Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States; Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, United States. Electronic address:

Acid-base homeostasis and pH regulation are critical for normal tissue metabolism and physiology, and brain tissue pH alters in many diseased states. Several noninvasive tissue pH Magnetic Resonance (MR) techniques have been developed over the past few decades to shed light on pH change during tissue function and dysfunction. Nevertheless, there are still challenges for mapping brain pH noninvasively at high spatiotemporal resolution. To address this unmet biomedical need, chemical exchange saturation transfer (CEST) MR techniques have been developed as a sensitive means for non-invasive pH mapping. This article briefly reviews the basic principles of different pH measurement techniques with a focus on CEST imaging of pH. Emerging pH imaging applications in the tumor are provided as examples throughout the narrative, and CEST pH imaging in acute stroke is discussed in the final section.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroscience.2021.01.026DOI Listing
January 2021

Quasi-steady state chemical exchange saturation transfer (QUASS CEST) analysis-correction of the finite relaxation delay and saturation time for robust CEST measurement.

Authors:
Phillip Zhe Sun

Magn Reson Med 2021 06 23;85(6):3281-3289. Epub 2021 Jan 23.

Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.

Purpose: CEST provides a MR contrast mechanism sensitizing to the exchange between dilute labile and bulk water protons. However, the CEST effect depends on the RF saturation duration and relaxation delay, which need to be long to reach its steady state. Our study aims to estimate the QUAsi-Steady State (QUASS) CEST signal from experiments with shorter saturation and relaxation delay times.

Methods: The evolution of the CEST signal was modeled as a function of the bulk water longitudinal relaxation rate during the relaxation delay (Td) and spin-lock relaxation rate during the RF saturation (Ts), from which the QUASS CEST effect is solved. Numeric simulations were programmed to compare the apparent CEST and QUASS CEST effects as a function of Ts and Td times. We also performed CEST MRI experiments from a creatine-gel pH phantom under serially varied Ts and Td times.

Results: The numeric simulation showed that although the apparent CEST effect depends on Td and Ts, the QUASS CEST solution has little dependence. Phantom results showed that the routine CEST pH contrast could be described by a nonlinear regression model (ie, ). We had = (P < 5e-8) and (P < 5e-6). For the QUASS CEST analysis, we modeled the pH contrast as , using a linear regression model. We had (P < 5e-9) and (P < 0.01), the slope of which is minimal.

Conclusions: The QUASS CEST algorithm provides a post-processing solution that facilitates robust CEST measurement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mrm.28653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224471PMC
June 2021

Low-density lipoprotein receptor-related protein-1 (LRP1) targeting contrast-enhanced MRI as a novel strategy for epilepsy imaging.

EBioMedicine 2021 Feb 22;64:103212. Epub 2021 Jan 22.

Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States; Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States; Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, United States. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2021.103212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823197PMC
February 2021

Analysis Protocol for the Quantification of Renal pH Using Chemical Exchange Saturation Transfer (CEST) MRI.

Methods Mol Biol 2021 ;2216:667-688

Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.

The kidney plays a major role in maintaining body pH homeostasis. Renal pH, in particular, changes immediately following injuries such as intoxication and ischemia, making pH an early biomarker for kidney injury before the symptom onset and complementary to well-established laboratory tests. Because of this, it is imperative to develop minimally invasive renal pH imaging exams and test pH as a new diagnostic biomarker in animal models of kidney injury before clinical translation. Briefly, iodinated contrast agents approved by the US Food and Drug Administration (FDA) for computed tomography (CT) have demonstrated promise as novel chemical exchange saturation transfer (CEST) MRI agents for pH-sensitive imaging. The generalized ratiometric iopamidol CEST MRI analysis enables concentration-independent pH measurement, which simplifies in vivo renal pH mapping. This chapter describes quantitative CEST MRI analysis for preclinical renal pH mapping, and their application in rodents, including normal conditions and acute kidney injury.This publication is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This analysis protocol chapter is complemented by two separate chapters describing the basic concepts and experimental procedure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-1-0716-0978-1_40DOI Listing
March 2021

Renal pH Mapping Using Chemical Exchange Saturation Transfer (CEST) MRI: Experimental Protocol.

Methods Mol Biol 2021 ;2216:455-471

Division of MR Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Chemical exchange saturation transfer (CEST) is recognized as one of the premier methods for measuring pH with this environmental variable expected to be an excellent biomarker for kidney diseases. Here we describe step-by-step CEST MRI experimental protocols for producing pH and perfusion maps for monitoring kidney pH homeostasis in rodents after administering iopamidol as contrast agent. Several CEST techniques, acquisition protocols and ratiometric approaches are described. The impact of length of acquisition time on the quality of the maps is detailed. These methods may be useful for investigating progression in kidney disease in vivo for rodent models.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This experimental protocol is complemented by two separate chapters describing the basic concepts and data analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-1-0716-0978-1_27DOI Listing
March 2021

Renal pH Imaging Using Chemical Exchange Saturation Transfer (CEST) MRI: Basic Concept.

Methods Mol Biol 2021 ;2216:241-256

F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA.

Magnetic Resonance Imaging (MRI) has been actively explored in the last several decades for assessing renal function by providing several physiological information, including glomerular filtration rate, renal plasma flow, tissue oxygenation and water diffusion. Within MRI, the developing field of chemical exchange saturation transfer (CEST) has potential to provide further functional information for diagnosing kidney diseases. Both endogenous produced molecules as well as exogenously administered CEST agents have been exploited for providing functional information related to kidney diseases in preclinical studies. In particular, CEST MRI has been exploited for assessing the acid-base homeostasis in the kidney and for monitoring pH changes in several disease models. This review summarizes several CEST MRI procedures for assessing kidney functionality and pH, for monitoring renal pH changes in different kidney injury models and for evaluating renal allograft rejection.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-1-0716-0978-1_14DOI Listing
March 2021

Refined Ischemic Penumbra Imaging with Tissue pH and Diffusion Kurtosis Magnetic Resonance Imaging.

Transl Stroke Res 2020 Nov 7. Epub 2020 Nov 7.

Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, 30329, USA.

Imaging has played a vital role in our mechanistic understanding of acute ischemia and the management of acute stroke patients. The most recent DAWN and DEFUSE-3 trials showed that endovascular therapy could be extended to a selected group of late-presenting stroke patients with the aid of imaging. Although perfusion and diffusion MRI have been commonly used in stroke imaging, the approximation of their mismatch as the penumbra is oversimplified, particularly in the era of endovascular therapy. Briefly, the hypoperfusion lesion includes the benign oligemia that does not proceed to infarction. Also, with prompt and effective reperfusion therapy, a portion of the diffusion lesion is potentially reversible. Therefore, advanced imaging that provides improved ischemic tissue characterization may enable new experimental stroke therapeutics and eventually further individualize stroke treatment upon translation to the clinical setting. Specifically, pH imaging captures tissue of altered metabolic state that demarcates the hypoperfused lesion into ischemic penumbra and benign oligemia, which remains promising to define the ischemic penumbra's outer boundary. On the other hand, diffusion kurtosis imaging (DKI) differentiates the most severely damaged and irreversibly injured diffusion lesion from the portion of diffusion lesion that is potentially reversible, refining the inner boundary of the penumbra. Altogether, the development of advanced imaging has the potential to not only transform the experimental stroke research but also aid clinical translation and patient management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12975-020-00868-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102648PMC
November 2020

Development of fast multi-slice apparent T mapping for improved arterial spin labeling MRI measurement of cerebral blood flow.

Magn Reson Med 2021 03 24;85(3):1571-1580. Epub 2020 Sep 24.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.

Purpose: To develop fast multi-slice apparent T (T ) mapping for accurate cerebral blood flow (CBF) quantification with arterial spin labeling (ASL) MRI.

Methods: Fast multi-slice T was measured using a modified inversion recovery echo planar imaging (EPI) sequence with simultaneous application of ASL tagging radiofrequency (RF) and gradient pulses. The fast multi-slice T measurement was compared with the single-slice T imaging approach, repeated per slice. CBF was assessed in healthy adult Wistar rats (N = 5) and rats with acute stroke 24 hours after a transient middle cerebral artery occlusion (N = 5).

Results: The fast multi-slice T measurement was in good agreement with that of a single-slice T imaging approach (Lin's concordance correlation coefficient = 0.92). CBF calculated using T reasonably accounted for the finite labeling RF duration, whereas the routine T -normalized ASL MRI underestimated the CBF, particularly at short labeling durations. In acute stroke rats, the labeling time and the CBF difference (ΔCBF) between the contralateral normal area and the ischemic lesion were significantly correlated when using T -normalized perfusion calculation (R = 0.844, P = .035). In comparison, T -normalized ΔCBF had little labeling time dependence based on the linear regression equation of ΔCBF = -0.0247*τ + 1.579 mL/g/min (R = -0.352, P = .494).

Conclusions: Our study found fast multi-slice T imaging improves the accuracy and reproducibility of CBF measurement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mrm.28510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718392PMC
March 2021

Investigating the origin of pH-sensitive magnetization transfer ratio asymmetry MRI contrast during the acute stroke: Correction of T change reveals the dominant amide proton transfer MRI signal.

Magn Reson Med 2020 11 16;84(5):2702-2712. Epub 2020 May 16.

Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.

Purpose: Amide proton transfer (APT) MRI is promising to serve as a surrogate metabolic imaging biomarker of acute stroke. Although the magnetization transfer ratio asymmetry (MTR ) has been used commonly, the origin of pH-weighted MRI effect remains an area of investigation, including contributions from APT, semisolid MT contrast asymmetry, and nuclear Overhauser enhancement effects. Our study aimed to determine the origin of pH-weighted MTR contrast following acute stroke.

Methods: Multiparametric MRI, including T , T , diffusion and Z-spectrum, were performed in rats after middle cerebral artery occlusion. We analyzed the conventional Z-spectrum and the apparent exchange spectrum , being the difference between the relaxation-scaled inverse Z-spectrum and the intrinsic spinlock relaxation rate . The ischemia-induced change was calculated as the spectral difference between the diffusion lesion and the contralateral normal area.

Results: The conventional Z-spectrum signal change at -3.5 ppm dominates that at +3.5 ppm (-1.16 ± 0.39% vs. 0.76 ± 0.26%, P < .01) following acute stroke. In comparison, the magnitude of ΔR change at 3.5 ppm becomes significantly larger than that at -3.5 ppm (-2.80 ± 0.40% vs. -0.94 ± 0.80%, P < .001), with their SNR being 7.0 and 1.2, respectively. We extended the magnetization transfer and relaxation normalized APT concept to the apparent exchange-dependent relaxation image, documenting an enhanced pH contrast between the ischemic lesion and the intact tissue, over that of MTR .

Conclusion: Our study shows that after the relaxation-effect correction, the APT effect is the dominant contributing factor to pH-weighted MTR following acute stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mrm.28313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402019PMC
November 2020

Demonstration of magnetization transfer and relaxation normalized pH-specific pulse-amide proton transfer imaging in an animal model of acute stroke.

Authors:
Phillip Zhe Sun

Magn Reson Med 2020 09 20;84(3):1526-1533. Epub 2020 Feb 20.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.

Purpose: pH-weighted amide proton transfer (APT) MRI is promising to serve as a new surrogate metabolic imaging biomarker for refined ischemic tissue demarcation. APT MRI with pulse-RF irradiation (pulse-APT) is an alternative to the routine continuous wave (CW-) APT MRI that overcomes the RF duty cycle limit. Our study aimed to generalize the recently developed pH-specific magnetization transfer and relaxation-normalized APT (MRAPT) analysis to pulse-APT MRI in acute stroke imaging.

Methods: Multiparametric MRI, including CW- and pulse-APT MRI scans, were performed following middle cerebral artery occlusion in rats. We calculated pH-sensitive MTR and pH-specific MRAPT contrast between the ipsilateral diffusion lesion and contralateral normal area.

Results: An inversion pulse of 10 to 15 ms maximizes the pH-sensitive MRI contrast for pulse-APT MRI. The contrast-to-noise ratio of pH-specific MRAPT effect between the contralateral normal area and ischemic lesion from both methods are comparable (3.25 ± 0.65 vs. 3.59 ± 0.40, P > .05). pH determined from both methods were in good agreement, with their difference within 0.1.

Conclusions: Pulse-APT MRI provides highly pH-specific mapping for acute stroke imaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mrm.28223DOI Listing
September 2020

Improved MR fingerprinting for relaxation measurement in the presence of semisolid magnetization transfer.

Magn Reson Med 2020 08 3;84(2):727-737. Epub 2020 Jan 3.

Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia.

Purpose: To characterize and minimize the magnetization transfer (MT) effect in MR fingerprinting (MRF) relaxation measurements with a 2-pool (2P) MT model of multiple tissue types.

Theory And Methods: Semisolid MT effect in MRF was modeled using 2P Bloch-McConnell equations. The combinations of MT parameters of multiple tissues (white [WM] and gray matter [GM]) were used to build the MRF dictionary. Both 1-pool (1P) and 2P models were simulated to characterize the dependence on MT. Relaxations measured using MRF with spin-echo saturation-recovery (SR) or inversion-recovery preparations were compared with conventional SR-prepared T and multiple spin-echo T measurements. The simulations results were validated with phantoms and brain tissue samples.

Results: The MRF signal was different from the 1P and 2P models. 1P MRF produced significantly (P < .05) underestimated T in WM (20-30%) and GM (7-10%), while 2P MRF measured consistent T and T in both WM and GM with conventional measurements (pairwise test P > .1; correlated P < .05). Simulations showed that SR-prepared MRF measuring T had much less errors against the variation of the macromolecular fraction. Compared with inversion-recovery preparation, SR-prepared MRF produced higher relaxation correlations (R > 0.9) with conventional measurements in both WM and GM across samples, suggesting that SR-prepared MRF was less sensitive to the compositive effect of multiple MT parameters variations.

Conclusions: 2P MRF using a combination of MT parameters for multiple tissue types can measure consistent relaxations with conventional methods. With the 2P models, SR-prepared MRF would provide an option for robust relaxation measurement under heterogeneous MT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mrm.28159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180097PMC
August 2020

Preliminary evaluation of dynamic glucose enhanced MRI of the human placenta during glucose tolerance test.

Quant Imaging Med Surg 2019 Oct;9(10):1619-1627

Fetal-Neonatal Neuroimaging and Developmental Science Center, Boston Children's Hospital, Boston, MA, USA.

Background: To investigate dynamic glucose enhanced (DGE) chemical exchange saturation transfer (CEST) MRI as a means to non-invasively image glucose transport in the human placenta.

Methods: Continuous wave (CW) CEST MRI was performed at 3.0 Tesla. The glucose contrast enhancement (GCE) was calculated based on the magnetization transfer asymmetry (MTRasym), and the DGE was calculated with the positive side of Z-spectra in reference to the first time point. The glucose CEST (GlucoCEST) was optimized using a glucose solution phantom. Glucose solution perfused placenta tissue was used to demonstrate GlucoCEST MRI effect. The vascular density of placental tissue was evaluated with yellow dye after MRI scans. Finally, we preliminarily demonstrated GlucoCEST MRI in five pregnant subjects who received a glucose tolerance test. For human studies, the dynamic R2* change was captured with T2*-weighted echo planar imaging (EPI).

Results: The GCE effect peaks at a saturation B1 field of about 2 μT, and the GlucoCEST effect increases linearly with the glucose concentration between 4-20 mM. In tissue, the GlucoCEST MRI was sensitive to the glucose perfusate and the placenta vascular density. Although the GCE baseline was sensitive to field inhomogeneity and motion artifacts, the temporal evolution of the GlucoCEST effect showed a consistent and positive response after oral glucose tolerance drink.

Conclusions: Despite the challenges of placental motion and field inhomogeneity, our study demonstrated the feasibility of DGE placenta MRI at 3.0 Tesla.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/qims.2019.09.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828580PMC
October 2019

Fast correction of B field inhomogeneity for pH-specific magnetization transfer and relaxation normalized amide proton transfer imaging of acute ischemic stroke without Z-spectrum.

Authors:
Phillip Zhe Sun

Magn Reson Med 2020 05 21;83(5):1688-1697. Epub 2019 Oct 21.

Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

Purpose: The magnetization transfer and relaxation normalized amide proton transfer (MRAPT) analysis is promising to provide a highly pH-specific mapping of tissue acidosis, complementing commonly used CEST asymmetry analysis. We aimed to develop a fast B inhomogeneity correction algorithm for acute stroke magnetization transfer and relaxation normalized amide proton transfer imaging without Z-spectral interpolation.

Methods: The proposed fast field inhomogeneity correction describes B artifacts with linear regression. We compared the new algorithm with the routine interpolation correction approach in CEST imaging of a dual-pH phantom. The fast B correction was further evaluated in amide proton transfer imaging of normal and acute stroke rats.

Results: Our phantom data showed that the proposed fast B inhomogeneity correction significantly improved pH MRI contrast, recovering over 80% of the pH MRI contrast-to-noise-ratio difference between the raw magnetization transfer ratio asymmetry and that using the routine interpolation-based B correction approach. In normal rat brains, the proposed fast B correction improved pH-specific MRI uniformity across the intact tissue, with the ratio of magnetization transfer and relaxation normalized amide proton transfer ratio being 10% of that without B inhomogeneity correction. In acute stroke rats, fast B inhomogeneity-corrected pH MRI reveals substantially improved pH lesion conspicuity, particularly in regions with nonnegligible B inhomogeneity. The pH MRI contrast-to-noise ratio between the ipsilateral diffusion lesion and contralateral normal tissue improved significantly with fast B correction (from 1.88 ± 0.48 to 2.20 ± 0.44, P < .01).

Conclusions: Our study established an expedient B inhomogeneity correction algorithm for fast pH imaging of acute ischemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mrm.28040DOI Listing
May 2020

Development of intravoxel inhomogeneity correction for chemical exchange saturation transfer spectral imaging: a high-resolution field map-based deconvolution algorithm for magnetic field inhomogeneity correction.

Authors:
Phillip Zhe Sun

Magn Reson Med 2020 04 19;83(4):1348-1355. Epub 2019 Oct 19.

Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia.

Purpose: CEST MRI is sensitive to dilute proteins/peptides and microenvironmental properties yet susceptible to magnetic field inhomogeneity. We aimed to develop a high-resolution field map-based CEST intravoxel inhomogeneity correction (CIVIC) algorithm for CEST Z-spectral imaging.

Methods: The proposed CIVIC approach treats the intravoxel inhomogeneity as a point spread function and applies the deconvolution algorithm to reconstruct the original Z-spectrum. We simulated the effect of B field inhomogeneity on CEST measurement and tested the efficacy of the proposed CIVIC algorithm. We also performed CEST MRI on a dual-pH Creatine-gel phantom under varied field homogeneity conditions and compared the CEST MRI contrast-to-noise ratio from the raw Z-spectrum, water saturation shift referencing, and the proposed CIVIC methods.

Results: The numerical simulation showed that the CIVIC algorithm remains effective even in the case of symmetric field dispersion with a 0 mean shift. The experimental results confirmed that the proposed CIVIC method substantially improves the CEST MRI contrast-to-noise ratio under different field homogeneity conditions.

Conclusion: Our study established a new intravoxel B inhomogeneity correction algorithm, promising to facilitate CEST spectral imaging in challenging experimental conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mrm.28015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949390PMC
April 2020

Mapping tissue pH in an experimental model of acute stroke - Determination of graded regional tissue pH changes with non-invasive quantitative amide proton transfer MRI.

Neuroimage 2019 05 10;191:610-617. Epub 2019 Feb 10.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. Electronic address:

pH-weighted amide proton transfer (APT) MRI is sensitive to tissue pH change during acute ischemia, complementing conventional perfusion and diffusion stroke imaging. However, the currently used pH-weighted magnetization transfer (MT) ratio asymmetry (MTR) analysis is of limited pH specificity. To overcome this, MT and relaxation normalized APT (MRAPT) analysis has been developed that to homogenize the background signal, thus providing highly pH conspicuous measurement. Our study aimed to calibrate MRAPT MRI toward absolute tissue pH mapping and determine regional pH changes during acute stroke. Using middle cerebral artery occlusion (MCAO) rats, we performed lactate MR spectroscopy and multi-parametric MRI. MRAPT MRI was calibrated against a region of interest (ROI)-based pH spectroscopy measurement (R = 0.70, P < 0.001), showing noticeably higher correlation coefficient than the simplistic MTR index. Capitalizing on this, we mapped brain tissue pH and semi-automatically segmented pH lesion, in addition to routine perfusion and diffusion lesions. Tissue pH from regions of the contralateral normal, perfusion/diffusion lesion mismatch and diffusion lesion was found to be 7.03 ± 0.04, 6.84 ± 0.10, 6.52 ± 0.19, respectively. Most importantly, we delineated the heterogeneous perfusion/diffusion lesion mismatch into perfusion/pH and pH/diffusion lesion mismatches, with their pH being 7.01 ± 0.04 and 6.71 ± 0.12, respectively (P < 0.05). To summarize, our study calibrated pH-sensitive MRAPT MRI toward absolute tissue pH mapping, semi-automatically segmented and determined graded tissue pH changes in ischemic tissue and demonstrated its feasibility for refined demarcation of heterogeneous metabolic disruption following acute stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2019.02.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440806PMC
May 2019

Direct radiofrequency saturation corrected amide proton transfer tumor MRI at 3T.

Magn Reson Med 2019 04 3;81(4):2710-2719. Epub 2018 Nov 3.

Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China.

Purpose: Amide proton transfer (APT) imaging has been increasingly applied in tumor characterization that complements diffusion and dynamic contrast-enhanced MRI. However, quantification of in vivo APT effect is challenging because of concomitant semisolid magnetization transfer (MT) and nuclear overhauser enhancement effects. A direct saturation corrected (DISC) chemical exchange saturation transfer (CEST) analysis has been recently proposed that simplifies the determination of in vivo CEST effects. Our present study aimed to extend the DISC analysis to pulsed radiofrequency CEST MRI and evaluate it at 3T.

Methods: Nine adult male Sprague-Dawley rats implanted C6 gliomas underwent multiparametric MRI of T , T , CEST, and T -weighted gadolinium-enhanced imaging 1 day before and 3 days after chemoradiotherapy. The routine MT asymmetry, 3-point method, and the extended DISC analysis were compared in tumor characterization with histology as a reference. Regional variations were assessed by 1-way analysis of variance.

Results: T , T , and MT asymmetry and the DISC CEST effects showed significant alterations in tumor/necrosis with respect to the contralateral reference (P < 0.05). The resolved APT effect revealed a significant difference among the contralateral reference (2.42 ± 0.24%), necrosis (2.86 ± 0.19%), and tumor (3.25 ± 0.15%) regions after chemoradiotherapy (P < 0.05), consistent with histological observations. Conversely, the MT asymmetry did not show tumor regional variation post-treatment (P > 0.05), whereas the 3-point method detected no regional alteration at both time points (P > 0.05).

Conclusion: Our study translated DISC CEST MRI to 3T, evaluated it in glioma rat models, and confirmed its advantages in resolving tumor heterogeneity over the routine asymmetry and 3-point analyses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mrm.27562DOI Listing
April 2019

Preliminary evaluation of accelerated microscopic diffusional kurtosis imaging (μDKI) in a rodent model of epilepsy.

Magn Reson Imaging 2019 02 20;56:90-95. Epub 2018 Oct 20.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States of America; Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States of America; Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, United States of America. Electronic address:

Purpose: Our study aimed to develop accelerated microscopic diffusional kurtosis imaging (μDKI) and preliminarily evaluated it in a rodent model of chronic epilepsy.

Methods: We investigated two μDKI acceleration schemes of reduced sampling density and angular range in a phantom and wild-type rats, and further tested μDKI method in pilocarpine-induced epilepsy rats using a 4.7 Tesla MRI. Single slice average μD and μK maps were derived, and Nissl staining was obtained.

Results: The kurtosis maps from two accelerated μDKI sampling schemes (sampling density and range) are very similar to that using fully sampled data (SSIM > 0.95). For the epileptic models, μDKI showed noticeably different contrast from those obtained with conventional DKI. Specifically, the average μK was significantly less than that of the average of K (0.15 ± 0.01 vs. 0.47 ± 0.02) in the ventricle.

Conclusions: Our study demonstrated the feasibility of accelerated in vivo μDKI. Our work revealed that μDKI provides complementary information to conventional DKI method, suggesting that advanced DKI sequences are promising to elucidate tissue microstructure in neurological diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mri.2018.10.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583913PMC
February 2019

In vivo microscopic diffusional kurtosis imaging with symmetrized double diffusion encoding EPI.

Magn Reson Med 2019 01 9;81(1):533-541. Epub 2018 Sep 9.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts.

Purpose: Diffusional kurtosis imaging (DKI) measures the deviation of the displacement probability from a normal distribution, complementing the data commonly acquired by diffusion MRI. It is important to elucidate the sources of kurtosis contrast, particularly in biological tissues where microscopic kurtosis (intrinsic kurtosis) and diffusional heterogeneity may co-exist.

Methods: We have developed a technique for microscopic kurtosis MRI, dubbed microscopic diffusional kurtosis imaging (µDKI), using a symmetrized double diffusion encoding (s-DDE) EPI sequence. We compared this newly developed µDKI to conventional DKI methods in both a triple compartment phantom and in vivo.

Results: Our results showed that whereas conventional DKI and µDKI provided similar measurements in a compartment of monosphere beads, kurtosis measured by µDKI was significantly less than that measured by conventional DKI in a compartment of mixed Gaussian pools. For in vivo brain imaging, µDKI showed small yet significantly lower kurtosis measurement in regions of the cortex, CSF, and internal capsule compared to the conventional DKI approach.

Conclusions: Our study showed that µDKI is less susceptible than conventional DKI to sub-voxel diffusional heterogeneity. Our study also provided important preliminary demonstration of our technique in vivo, warranting future studies to investigate its diagnostic use in examining neurological disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mrm.27419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258297PMC
January 2019

Determination of multipool contributions to endogenous amide proton transfer effects in global ischemia with high spectral resolution in vivo chemical exchange saturation transfer MRI.

Magn Reson Med 2019 01 29;81(1):645-652. Epub 2018 Jul 29.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts.

Purpose: Chemical exchange saturation transfer (CEST) MRI has been used for quantitative assessment of dilute metabolites and/or pH in disorders such as acute stroke and tumor. However, routine asymmetry analysis (MTR ) may be confounded by concomitant effects such as semisolid macromolecular magnetization transfer (MT) and nuclear Overhauser enhancement. Resolving multiple contributions is essential for elucidating the origins of in vivo CEST contrast.

Methods: Here we used a newly proposed image downsampling expedited adaptive least-squares fitting on densely sampled Z-spectrum to quantify multipool contribution from water, nuclear Overhauser enhancement, MT, guanidinium, amine, and amide protons in adult male Wistar rats before and after global ischemia.

Results: Our results revealed the major contributors to in vivo T -normalized MTR (3.5 ppm) contrast between white and gray matter (WM/GM) in normal brain (-1.96%/second) are pH-insensitive macromolecular MT (-0.89%/second) and nuclear Overhauser enhancement (-1.04%/second). Additionally, global ischemia resulted in significant changes of MTR , being -2.05%/second and -1.56%/second in WM and GM, which are dominated by changes in amide (-1.05%/second, -1.14%/second) and MT (-0.88%/second, -0.62%/second). Notably, the pH-sensitive amine and amide effects account for nearly 60% and 80% of the MTR changes seen in WM and GM, respectively, after global ischemia, indicating that MTR is predominantly pH-sensitive.

Conclusion: Combined amide and amine effects dominated the MTR changes after global ischemia, indicating that MTR is predominantly pH-sensitive and suitable for detecting tissue acidosis following acute stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mrm.27385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258351PMC
January 2019

Within-subject test-retest reliability of the atlas-based cortical volume measurement in the rat brain: A voxel-based morphometry study.

J Neurosci Methods 2018 09 28;307:46-52. Epub 2018 Jun 28.

Department of Neurobiology, Capital Medical University, Beijing, China. Electronic address:

Background: Various neurological and psychological disorders are related to cortical volume changes in specific brain regions, which can be measured in vivo using structural magnetic resonance imaging (sMRI). There is an increasing interest in MRI studies using rat models, especially in longitudinal studies of brain disorders and pharmacologic interventions. However, morphometric changes observed in sMRI are only meaningful if the measurements are reliable. To date, a systematic evaluation of the test-retest reliability of the morphometric measures in the rat brain is still lacking.

New Method: We rigorously evaluated the test-retest reliability of morphometric measures derived from the voxel-based morphometry (VBM) analysis. 37 Sprague-Dawley rats were scanned twice at an interval of six hours and the gray matter volume was estimated using the VBM-DARTEL method. The intraclass coefficient, percent volume change and Pearson correlation coefficient were used to evaluate the reliability in 96 subregions of the rat brain.

Results: Most subregions showed excellent test-retest reliabilities within an interval of 6 h while a few regions demonstrated lower reliability, especially in the retrosplenial granular cortex. The results were consistent between different methods of reliability assessment.

Comparison With Existing Method: To the best of our knowledge, this is the first study to quantify the test-retest reliability of the VBM measurements of the rat brain.

Conclusion: Atlas-based cortical volume of the rat brain can be reliably estimated using the VBM-DARTEL method in most subregions. However, findings in subregions with lower reliability must be interpreted with caution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jneumeth.2018.06.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461491PMC
September 2018

Noninvasive magnetic resonance/photoacoustic imaging for photothermal therapy response monitoring.

Nanoscale 2018 Mar;10(13):5864-5868

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.

In vivo assessment of vascular permeability and therapeutic response provides novel insights into photothermal therapy (PTT) that is currently under clinical investigation. We have developed noninvasive imaging strategies to improve the monitoring of nanoparticle-mediated PTT responses for personalized nanomedicine. Briefly, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and photoacoustic imaging (PAI) were applied to study the enhanced permeability and retention (EPR) effect in tumor models of different microvascular permeabilities (i.e., 4T1 mouse breast tumor model and HUH-7 human hepatoma model in nude mice). Magnetic resonance temperature imaging (MRTI) and diffusion-weighted MRI (DWI) showed that the 4T1 tumor model exhibits a higher PTT temperature response than that of the HUH-7 tumor model. Our findings demonstrate that the combined use of MRI and PAI techniques is useful in monitoring the vascular permeability and temperature status following PTT, promising to help guide PTT in future translational investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/C8NR00044ADOI Listing
March 2018

Diffusion Kurtosis Imaging of Acute Infarction: Comparison with Routine Diffusion and Follow-up MR Imaging.

Radiology 2018 05 20;287(2):651-657. Epub 2018 Mar 20.

From the Departments of Radiology (J.Y., H.N., W.S.) and Neurology (Z.W.), Tianjin First Central Hospital, Tianjin, China; Department of Medicine, Tianjin Medical University, Tianjin, China (H.S.); and Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, 149 13th St, Room 2301 CNY, Charlestown, MA 02129 (P.Z.S.).

Purpose To determine the relationship between diffusion-weighted imaging (DWI) and diffusion kurtosis imaging (DKI) in patients with acute stroke at admission and the tissue outcome 1 month after onset of stroke. Materials and Methods Patients with stroke underwent DWI (b values = 0, 1000 sec/mm along three directions) and DKI (b values = 0, 1000, 2000 sec/mm along 20 directions) within 24 hours after symptom onset and 1 month after symptom onset. For large lesions (diameter ≥ 1 cm), acute lesion volumes at DWI and DKI were compared with those at follow-up T2-weighted imaging by using Spearman correlation analysis. For small lesions (diameter < 1 cm), the number of acute lesions at DWI and DKI and follow-up T2-weighted imaging was counted and compared by using the McNemar test. Results Thirty-seven patients (mean age, 58 years; range, 35-82 years) were included. There were 32 large lesions and 138 small lesions. For large lesions, the volumes of acute lesions on kurtosis maps showed no difference from those on 1-month follow-up T2-weighted images (P = .532), with a higher correlation coefficient than those on the apparent diffusion coefficient and mean diffusivity maps (R = 0.730 vs 0.479 and 0.429). For small lesions, the number of acute lesions on DKI, but not on DWI, images was consistent with that on the follow-up T2-weighted images (P = .125). Conclusion DKI complements DWI for improved prediction of outcome of acute ischemic stroke. RSNA, 2018.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2017170553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5929367PMC
May 2018

JOURNAL CLUB: Evaluation of Diffusion Kurtosis Imaging of Stroke Lesion With Hemodynamic and Metabolic MRI in a Rodent Model of Acute Stroke.

AJR Am J Roentgenol 2018 Apr 22;210(4):720-727. Epub 2018 Feb 22.

1 Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, 149 13th St, Rm 2301, Charlestown, MA 02129.

Objective: Diffusion kurtosis imaging (DKI) has emerged as a new acute stroke imaging approach, augmenting routine DWI. Although it has been shown that a diffusion lesion without kurtosis abnormality is more likely to recover after reperfusion, whereas a kurtosis lesion shows poor response, little is known about the underlying pathophysiologic profile of the kurtosis lesion versus the kurtosis lesion-diffusion lesion mismatch.

Materials And Methods: We performed multiparametric MRI, including arterial spin labeling, pH-sensitive amide proton transfer, and DKI, in a rodent model of acute stroke caused by embolic middle cerebral artery occlusion. Diffusion and kurtosis lesions were semiautomatically segmented, and multiparametric MRI indexes were compared among the kurtosis lesion, diffusion lesion, kurtosis lesion-diffusion lesion mismatch, and the contralateral normal tissue area.

Results: We confirmed a significant difference between diffusion lesion and kurtosis lesion volumes (mean [± SD] volume, 151 ± 65 vs 125 ± 47 mm; p < 0.05). Although ischemic lesions have significantly reduced cerebral blood flow compared with contralateral normal tissue, we did not find a significant difference in cerebral blood flow between the kurtosis lesion and the kurtosis lesion-diffusion lesion mismatch (mean cerebral blood flow, 0.53 ± 0.10 vs 0.47 ± 0.14 mL/g of tissue per minute; p > 0.05). Of importance, the pH of the kurtosis lesion was significantly lower than that of the lesion mismatch (mean pH, 6.81 ± 0.08 vs 6.89 ± 0.09; p < 0.01).

Conclusion: The present study confirms that DKI provides an expedient approach for refining the heterogeneous DWI lesion that is associated with graded metabolic derangement, which is promising for improving the infarction core definition and ultimately helping to guide stroke treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2214/AJR.17.19134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814247PMC
April 2018

Direct saturation-corrected chemical exchange saturation transfer MRI of glioma: Simplified decoupling of amide proton transfer and nuclear overhauser effect contrasts.

Magn Reson Med 2017 Dec 13;78(6):2307-2314. Epub 2017 Oct 13.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.

Purpose: Chemical exchange saturation transfer (CEST) MRI has shown promise in tissue characterization in diseases like stroke and tumor. However, in vivo CEST imaging such as amide proton transfer (APT) MRI is challenging because of concomitant factors such as direct water saturation, macromolecular magnetization transfer, and nuclear overhauser effect (NOE), which lead to a complex contrast in the commonly used asymmetry analysis (MTRasym). Here, we propose a direct saturation-corrected CEST (DISC-CEST) analysis for simplified decoupling and quantification of in vivo CEST effects.

Methods: CEST MRI and relaxation measurements were carried out on a classical 2-pool creatine-gel CEST phantom and normal rat brains (N = 6) and a rat model of glioma (N = 8) at 4.7T. The proposed DISC-CEST quantification was carried out and compared with conventional MTRasym and the original three-offset method.

Results: We demonstrated that the DISC-CEST contrast in the phantom had much stronger correlation with MTRasym than the three-offset method, which showed substantial underestimation. In normal rat brains, the DISC-CEST approach revealed significantly stronger APT effect in gray matter and higher NOE effect in white matter. Furthermore, the APT and NOE maps derived from DISC-CEST showed significantly higher APT effect in the tumors than contralateral normal tissue but no apparent difference in NOE.

Conclusion: The proposed DISC-CEST method, by correction of nonlinear direct water saturation effect, serves as a promising alternative to both the commonly used MTRasym and the simplistic three-offset analyses. It provides simple yet reliable in vivo CEST quantification such as APT and NOE mapping in brain tumor, which is promising for clinical translation. Magn Reson Med 78:2307-2314, 2017. © 2017 International Society for Magnetic Resonance in Medicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mrm.26959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5744877PMC
December 2017

pH imaging reveals worsened tissue acidification in diffusion kurtosis lesion than the kurtosis/diffusion lesion mismatch in an animal model of acute stroke.

J Cereb Blood Flow Metab 2017 Oct 28;37(10):3325-3333. Epub 2017 Jul 28.

1 Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, USA.

Diffusion weighted imaging (DWI) has been commonly used in acute stroke examination, yet a portion of DWI lesion may be salvageable. Recently, it has been shown that diffusion kurtosis imaging (DKI) defines the most severely damaged DWI lesion that does not renormalize following early reperfusion. We postulated that the diffusion and kurtosis lesion mismatch experience heterogeneous hemodynamic and/or metabolic injury. We investigated tissue perfusion, pH, diffusion, kurtosis and relaxation from regions of the contralateral normal area, diffusion lesion, kurtosis lesion and their mismatch in an animal model of acute stroke. Our study revealed significant kurtosis and diffusion lesion volume mismatch (19.7 ± 10.7%, P < 0.01). Although there was no significant difference in perfusion and diffusion between the kurtosis lesion and kurtosis/diffusion lesion mismatch, we showed lower pH in the kurtosis lesion (pH = 6.64 ± 0.12) from that of the kurtosis/diffusion lesion mismatch (6.84 ± 0.11, P < 0.05). Moreover, pH in the kurtosis lesion and kurtosis/diffusion mismatch agreed well with literature values for regions of ischemic core and penumbra, respectively. Our work documented initial evidence that DKI may reveal the heterogeneous metabolic derangement within the commonly used DWI lesion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0271678X17721431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5624397PMC
October 2017
-->