Authors: F. Vega, A. Addeh, M.E. MacDonald
Journal: JCBFM Brain and Brain PET 2022 abstracts
Publication date: 2022/6

Authors: M. Ethan MacDonald, Eremiahs Fikre, Fernando Vega, AbdolJalil Addeh
Conference: International Society of Magnetic Resonance in Medicine
Publication date: 2022/5
In this work, the denoising autoencoder is applied to simulated low field, low resolution, low signal-to-noise images and used to recover the high field, high resolution, high signal-to-noise paired image. Different types of noise, gaussian and chi-squared, is added in simulation. We found that the denoising autoencoder worked slightly better for normally disturbed noise, but not in all cases. We found a linear trend between the model performance with RMSE and the standard deviation of the added noise. This work demonstrates the use of simple and robust denoising autoencoder to improve low field MRI.

Authors: Rebecca J Williams, Jacinta L Specht, M. Ethan MacDonald, G. Bruce Pike
Conference: International Society of Magnetic Resonance in Medicine
Publication date: 2022/5
Cerebrovascular reactivity (CVR) and task-based BOLD fMRI signals are closely linked. Understanding whether the relationship between CVR and task-based BOLD responses varies across the brain is important for interpreting BOLD, particularly in studies of aging where both CVR and BOLD activation differences are observed. Therefore, this work aimed to investigate the linear relationship between breath-hold (BH) CVR and task-based BOLD across the cerebral cortex to different cognitive tasks. Significant linear relationships were observed in posterior regions independent of task, while anterior regions were task-specific. These findings might contribute to understanding age-related posterior-anterior BOLD activation differences commonly observed in fMRI studies.

Authors: Deepthi Rajashekar, Matthias Wilms, M Ethan MacDonald, Serena Schimert, Michael D Hill, Andrew Demchuk, Mayank Goyal, Sean P Dukelow, Nils Daniel Forkert
Journal: Stroke and vascular neurology
Publication date: 2022/4/1
Publisher: BMJ Specialist Journals
Lesion-symptom mapping (LSM) is a statistical technique to investigate the population-specific relationship between structural integrity and post-stroke clinical outcome. In clinical practice, patients are commonly evaluated using the National Institutes of Health Stroke Scale (NIHSS), an 11-domain clinical score to quantitate neurological deficits due to stroke. So far, LSM studies have mostly used the total NIHSS score for analysis, which might not uncover subtle structure–function relationships associated with the specific sub-domains of the NIHSS evaluation. Thus, the aim of this work was to investigate the feasibility to perform LSM analyses with sub-score information to reveal category-specific structure–function relationships that a total score may not reveal.

Authors: Matthias Wilms, Jordan J Bannister, Pauline Mouches, M Ethan MacDonald, Deepthi Rajashekar, Sönke Langner, Nils D Forkert
Journal: IEEE Transactions on Medical Imaging
Publication date: 2022/3/24
Publisher: EEE
Many machine learning tasks in neuroimaging aim at modeling complex relationships between a brain’s morphology as seen in structural MR images and clinical scores and variables of interest. A frequently modeled process is healthy brain aging for which many image-based brain age estimation or age-conditioned brain morphology template generation approaches exist. While age estimation is a regression task, template generation is related to generative modeling. Both tasks can be seen as inverse directions of the same relationship between brain morphology and age. However, this view is rarely exploited and most existing approaches train separate models for each direction. In this paper, we propose a novel bidirectional approach that unifies score regression and generative morphology modeling and we use it to build a bidirectional brain aging model. We achieve this by defining an invertible normalizing flow architecture that learns a probability distribution of 3D brain morphology conditioned on age. The use of full 3D brain data is achieved by deriving a manifold-constrained formulation that models morphology variations within a low-dimensional subspace of diffeomorphic transformations. This modeling idea is evaluated on a database of MR scans of more than 5000 subjects. The evaluation results show that our bidirectional brain aging model (1) accurately estimates brain age, (2) is able to visually explain its decisions through attribution maps and counterfactuals, (3) generates realistic age-specific brain morphology templates, (4) supports the analysis of morphological variations, and (5) can be utilized for subject-specific brain aging simulation.

Authors: M Ethan MacDonald, G Bruce Pike
Journal: NMR in Biomedicine
Publication date: 2021/9
We present a review of the characterization of healthy brain aging using MRI with an emphasis on morphology, lesions, and quantitative MR parameters. A scope review found 6612 articles encompassing the keywords “Brain Aging” and “Magnetic Resonance”; papers involving functional MRI or not involving imaging of healthy human brain aging were discarded, leaving 2246 articles. We first consider some of the biogerontological mechanisms of aging, and the consequences of aging in terms of cognition and onset of disease. Morphological changes with aging are reviewed for the whole brain, cerebral cortex, white matter, subcortical gray matter, and other individual structures. In general, volume and cortical thickness decline with age, beginning in mid-life. Prevalent silent lesions such as white matter hyperintensities, microbleeds, and lacunar infarcts are also observed with increasing frequency. The literature regarding quantitative MR parameter changes includes T1, T2, T2*, magnetic susceptibility, spectroscopy, magnetization transfer, diffusion, and blood flow. We summarize the findings on how each of these parameters varies with aging. Finally, we examine how the aforementioned techniques have been used for age prediction. While relatively large in scope, we present a comprehensive review that should provide the reader with sound understanding of what MRI has been able to tell us about how the healthy brain ages.

Authors: Rebecca J Williams, M Ethan MacDonald, Erin L Mazerolle, G Bruce Pike
Journal: Frontiers in Physics
Publication date: 2021/4/12
Publisher: Frontiers
Elucidating the brain regions and networks associated with cognitive processes has been the mainstay of task-based fMRI, under the assumption that BOLD signals are uncompromised by vascular function. This is despite the plethora of research highlighting BOLD modulations due to vascular changes induced by disease, drugs, and aging. On the other hand, BOLD fMRI-based assessment of cerebrovascular reactivity (CVR) is often used as an indicator of the brain's vascular health and has been shown to be strongly associated with cognitive function. This review paper considers the relationship between BOLD-based assessments of CVR, cognition and task-based fMRI. How the BOLD response reflects both CVR and neural activity, and how findings of altered CVR in disease and in normal physiology are associated with cognition and BOLD signal changes are discussed. These are pertinent considerations for fMRI applications aiming to understand the biological basis of cognition. Therefore, a discussion of how the acquisition of BOLD-based CVR can enhance our ability to map human brain function, with limitations and potential future directions, is presented.

Authors: Lucas Lo Vercio, Kimberly Amador, Jordan J Bannister, Sebastian Crites, Alejandro Gutierrez, M Ethan MacDonald, Jasmine Moore, Pauline Mouches, Deepthi Rajashekar, Serena Schimert, Nagesh Subbanna, Anup Tuladhar, Nanjia Wang, Matthias Wilms, Anthony Winder, Nils D Forkert
Journal:J ournal of Neural Engineering
Publication date: 2020/11/19
Publisher: IOP Publishing
n an increasingly data-driven world, artificial intelligence is expected to be a key tool for converting big data into tangible benefits and the healthcare domain is no exception to this. Machine learning aims to identify complex patterns in multi-dimensional data and use these uncovered patterns to classify new unseen cases or make data-driven predictions. In recent years, deep neural networks have shown to be capable of producing results that considerably exceed those of conventional machine learning methods for various classification and regression tasks. In this paper, we provide an accessible tutorial of the most important supervised machine learning concepts and methods, including deep learning, which are potentially the most relevant for the medical domain. We aim to take some of the mystery out of machine learning and depict how machine learning models can be useful for medical applications. Finally, this tutorial provides a few practical suggestions for how to properly design a machine learning model for a generic medical problem.

Authors: M Ethan MacDonald, Rebecca J Williams, Deepthi Rajashekar, Randall B Stafford, Alexadru Hanganu, Hongfu Sun, Avery JL Berman, Cheryl R McCreary, Richard Frayne, Nils D Forkert, G Bruce Pike
Journal: Neurobiology of Aging
Publication date: 2020/11/1
Publisher: Elsevier
Cerebral cortex thinning and cerebral blood flow (CBF) reduction are typically observed during normal healthy aging. However, imaging-based age prediction models have primarily used morphological features of the brain. Complementary physiological CBF information might result in an improvement in age estimation. In this study, T1-weighted structural magnetic resonance imaging and arterial spin labeling CBF images were acquired in 146 healthy participants across the adult life span. Sixty-eight cerebral cortex regions were segmented, and the cortical thickness and mean CBF were computed for each region. Linear regression with age was computed for each region and data type, and laterality and correlation matrices were computed. Sixteen predictive models were trained with the cortical thickness and CBF data alone as well as a combination of both data types. The age explained more variance in the cortical thickness data (average R2 of 0.21) than in the CBF data (average R2 of 0.09). All 16 models performed significantly better when combining both measurement types and using feature selection, and thus, we conclude that the inclusion of CBF data marginally improves age estimation.

Authors: Matthias Wilms, Jordan J Bannister, Pauline Mouches, M Ethan MacDonald, Deepthi Rajashekar, Sönke Langner, Nils D Forkert
Book: Machine learning in clinical neuroimaging and radiogenomics in neuro-oncology
Publication date: 2020/10/4
Publisher: Springer, Cham
Brain aging is a widely studied longitudinal process throughout which the brain undergoes considerable morphological changes and various machine learning approaches have been proposed to analyze it. Within this context, brain age prediction from structural MR images and age-specific brain morphology template generation are two problems that have attracted much attention. While most approaches tackle these tasks independently, we assume that they are inverse directions of the same functional bidirectional relationship between a brain’s morphology and an age variable. In this paper, we propose to model this relationship with a single conditional normalizing flow, which unifies brain age prediction and age-conditioned generative modeling in a novel way. In an initial evaluation of this idea, we show that our normalizing flow brain aging model can accurately predict brain age while also being able to generate age-specific brain morphology templates that realistically represent the typical aging trend in a healthy population. This work is a step towards unified modeling of functional relationships between 3D brain morphology and clinical variables of interest with powerful normalizing flows.

Authors: Melany McLean, R Marc Lebel, M Ethan MacDonald, Mathieu Boudreau, G Bruce Pike
Conference: International Society of Magnetic Resonance in Medicine
Publication date: 2020/8
Quantitative magnetization transfer (qMT) is a Z-spectrum based imaging technique used to study white matter. The need to acquire many images with unique RF saturation pulses leads to long acquisition times. We aim to shorten qMT imaging times using a sparseSENSE technique that combines parallel imaging and compressed sensing to reduce the amount of acquired data. Retrospectively undersampled data was reconstructed for a range of acceleration factors using wavelet and total variation sparsifying domains. Pool size ratio (F) maps were accelerated by a factor of 4×, and acceleration factors of 8-12× may be possible in future work.

Authors: Hongfu Sun, M Ethan MacDonald, R Marc Lebel, G Bruce Pike
Publication date: 2020/7/24
Publisher: International Society for Magnetic Resonance in Medicine
A multi-echo MPRAGE sequence with radial fan-beam segments is demonstrated at 3 T. The radial fan-beam sampling scheme permits any number of encoding steps by adjusting the fan size for each inversion segment, which allows longer echo time for magnetic susceptibility contrast. Simultaneous T1-weighted image, R2* map, and QSM were successfully extracted from the single acquisition and were compared with images reconstructed from standard single-echo MPRAGE and multi-echo GRE acquisitions.

Authors: Deepthi Rajashekar, Matthias Wilms, M Ethan MacDonald, Jan Ehrhardt, Pauline Mouches, Richard Frayne, Michael D Hill, Nils D Forkert
Journal: Scientific Data
Publication date: 2020/2/17
Publisher: Nature Publishing Group
Normative brain atlases are a standard tool for neuroscience research and are, for example, used for spatial normalization of image datasets prior to voxel-based analyses of brain morphology and function. Although many different atlases are publicly available, they are usually biased with respect to an imaging modality and the age distribution. Both effects are well known to negatively impact the accuracy and reliability of the spatial normalization process using non-linear image registration methods. An important and very active neuroscience area that lacks appropriate atlases is lesion-related research in elderly populations (e.g. stroke, multiple sclerosis) for which FLAIR MRI and non-contrast CT are often the clinical imaging modalities of choice. To overcome the lack of atlases for these tasks and modalities, this paper presents high-resolution, age-specific FLAIR and non-contrast CT atlases of the elderly generated using clinical images.

Authors: M Ethan MacDonald, Rebecca J Williams, Nils D Forkert, Avery JL Berman, Cheryl R McCreary, Richard Frayne, G Bruce Pike
Journal: Cerebral Cortex
Publication date: 2019/7/22
Publisher: Oxford University Press
The phenomenon of cortical thinning with age has been well established; however, the measured rate of change varies between studies. The source of this variation could be image acquisition techniques including hardware and vendor specific differences. Databases are often consolidated to increase the number of subjects but underlying differences between these datasets could have undesired effects. We explore differences in cerebral cortex thinning between 4 databases, totaling 1382 subjects. We investigate several aspects of these databases, including: 1) differences between databases of cortical thinning rates versus age, 2) correlation of cortical thinning rates between regions for each database, and 3) regression bootstrapping to determine the effect of the number of subjects included. We also examined the effect of different databases on age prediction modeling. Cortical thinning rates were significantly different between databases in all 68 parcellated regions (ANCOVA, P < 0.001). Subtle differences were observed in correlation matrices and bootstrapping convergence. Age prediction modeling using a leave-one-out cross-validation approach showed varying prediction performance (0.64 < R2 < 0.82) between databases. When a database was used to calibrate the model and then applied to another database, prediction performance consistently decreased. We conclude that there are indeed differences in the measured cortical thinning rates between these large-scale databases.

Authors: M Ethan MacDonald, Wei-Qiao Liu, Sarah Scott, Conrad P Rockel, Deepthi Rajashekar, Jacinta L Specht, Hongfu Sun, G Bruce Pike
Conference: International Society of Magnetic Resonance in Medicine
Publication date: 2019/5
Lesions in multiple sclerosis (MS) present at various locations throughout the brain. 207 relapsing-remitting MS (RRMS) patients were scanned at 3T. T2w and T1w images were used to segment white matter (WM) hyper- and hypo-intensities, respectively. Using an atlas of WM tracts, the lesion burden was computed for each tract. The dominant lesion load was found in the periventricular regions. The tract percent load is highest in the anterior thalamic radiation, inferior fronto-occipital fasciculus, the forceps major, and forceps minor tracts. The uncinate fasciculus, superior longitudinal fasciculus, and the four cingulum tracts have the lowest lesion loads.

Authors: Hongfu Sun, M MacDonald, E Mazerolle, Kristin Sabourin, B Pike
Journal: Internal Society of Magnetic Resonance in Medicine 27th Annual Meeting and Exhibition, Montreal
Publication date: 2019
Precise localization of the internal globus pallidus (GPi) is critical for MRgFUS pallidotomy for movement disorders such as Parkinson’s disease. In this study, high-resolution FGATIR, R2* and QSM are compared for localizing GPi in six healthy subjects (age from 21 to 41). All three methods displayed some image contrasts in the GP area. QSM demonstrated the best delineation of GPi from the internal capsule, which is generally considered a risk zone for pallidotomy. GPi also appeared smaller in FGATIR, where GPi was hypointense, than in QSM, where GPi was hyperintense.

Authors: Hongfu Sun, Yuhan Ma, M Ethan MacDonald, G Bruce Pike
Journal: Neuroimage
Publication date: 2018/10/1
Publisher: Academic Press
A new dipole field inversion method for whole head quantitative susceptibility mapping (QSM) is proposed. Instead of performing background field removal and local field inversion sequentially, the proposed method performs dipole field inversion directly on the total field map in a single step. To aid this under-determined and ill-posed inversion process and obtain robust QSM images, Tikhonov regularization is implemented to seek the local susceptibility solution with the least-norm (LN) using the L-curve criterion. The proposed LN-QSM does not require brain edge erosion, thereby preserving the cerebral cortex in the final images. This should improve its applicability for QSM-based cortical grey matter measurement, functional imaging and venography of full brain. Furthermore, LN-QSM also enables susceptibility mapping of the entire head without the need for brain extraction, which makes QSM reconstruction more automated and less dependent on intermediate pre-processing methods and their associated parameters. It is shown that the proposed LN-QSM method reduced errors in a numerical phantom simulation, improved accuracy in a gadolinium phantom experiment, and suppressed artefacts in nine subjects, as compared to two-step and other single-step QSM methods. Measurements of deep grey matter and skull susceptibilities from LN-QSM are consistent with established reconstruction methods.

Authors: M Ethan MacDonald, Avery JL Berman, Erin L Mazerolle, Rebecca J Williams, G Bruce Pike
Journal: Neuroimage
Publication date: 2018/9/1
Publisher: Academic Press
A new method is proposed for obtaining cerebral perfusion measurements whereby blood oxygen level dependent (BOLD) MRI is used to dynamically monitor hyperoxia-induced changes in the concentration of deoxygenated hemoglobin in the cerebral vasculature. The data is processed using kinetic modeling to yield perfusion metrics, namely: cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). Ten healthy human subjects were continuously imaged with BOLD sequence while a hyperoxic (70% O2) state was interspersed with baseline periods of normoxia. The BOLD time courses were fit with exponential uptake and decay curves and a biophysical model of the BOLD signal was used to estimate oxygen concentration functions. The arterial input function was derived from end-tidal oxygen measurements, and a deconvolution operation between the tissue and arterial concentration functions was used to yield CBF. The venous component of the CBV was calculated from the ratio of the integrals of the estimated tissue and arterial concentration functions. Mean gray and white matter measurements were found to be: 61.6 ± 13.7 and 24.9 ± 4.0 ml 100 g−1 min−1 for CBF; 1.83 ± 0.32 and 1.10 ± 0.19 ml 100 g−1 for venous CBV; and 2.94 ± 0.52 and 3.73 ± 0.60 s for MTT, respectively. We conclude that it is possible to derive CBF, CBV and MTT metrics within expected physiological ranges via analysis of dynamic BOLD fMRI acquired during a period of hyperoxia.

Authors: Avery JL Berman, Erin L Mazerolle, M Ethan MacDonald, Nicholas P Blockley, Wen-Ming Luh, G Bruce Pike
Journal: Neuroimage
Publication date: 2018/4/1
Publisher: Academic Press
Calibrated functional magnetic resonance imaging (fMRI) is a method to independently measure the metabolic and hemodynamic contributions to the blood oxygenation level dependent (BOLD) signal. This technique typically requires the use of a respiratory challenge, such as hypercapnia or hyperoxia, to estimate the calibration constant, M. There has been a recent push to eliminate the gas challenge from the calibration procedure using asymmetric spin echo (ASE) based techniques. This study uses simulations to better understand spin echo (SE) and ASE signals, analytical modelling to characterize the signal evolution, and in vivo imaging to validate the modelling. Using simulations, it is shown how ASE imaging generally underestimates M and how this depends on several parameters of the acquisition, including echo time and ASE offset, as well as the vessel size. This underestimation is the result of imperfect SE refocusing due to diffusion of water through the extravascular environment surrounding the microvasculature. By empirically characterizing this SE attenuation as an exponential decay that increases with echo time, we have proposed a quadratic ASE biophysical signal model. This model allows for the characterization and compensation of the SE attenuation if SE and ASE signals are acquired at multiple echo times. This was tested in healthy subjects and was found to significantly increase the estimates of M across grey matter. These findings show promise for improved gas-free calibration and can be extended to other relaxation-based imaging studies of brain physiology.

Authors: M Ethan MacDonald, Nils D Forkert, Yuhan Ma, Rebecca J Williams, Alexandru Hanganu, Hongfu Sun, Randall Stafford, Cheryl R McCreary, Richard Frayne, G Bruce Pike
Publication date: 2018
Publisher: 26th ISMRM Scientific Meeting Paris, France
Changes in both cortical thickness and cerebral blood flow are observed with age. In this work, we look at how these parameters are modulated across the lifespan. T1-weighted and arterial spin labelling data from 146 subjects were analyzed, with 68 cortical regions selected in each subject to obtain mean cortical thickness and cerebral blood flow. We calculated rates of change, correlation, and laterality for both parameters. Finally, we explored predictive modeling using cortical thickness, CBF and a model combining the two. Predictive modelling was slightly improved when both measures were included.

Authors: Melany Mclean, Matthew Ethan MacDonald, R Marc Lebel, Mathieu Boudreau, Bruce Pike
Journal: Proceedings of the 25th Annual Meeting of ISMRM
Publication date: 2017/4/27

Authors: M Ethan MacDonald, Rebecca J Williams, Nils D Forkert, Avery JL Berman, Cheryl M McCreary, Richard Frayne, Bruce Pike
Journal: International Society of Magnetic Resonance in Medicine
Publication date: 2017/4
This work investigates cerebral cortical thinning as a function of age, and how this relationship varies between four healthy subject databases, with a consolidated 1,382 subjects. Cortical thickness measurements of each subject were computed for 68 regions. Linear regression was used to determine the thinning rate for each region in each database as well as for the consolidated database. ANCOVA tests were run to test the effect of database. Correlation matrices were used to test the intra-relationship of locations between databases. Statistically significant correlations were found with age and differences were found between databases in all regions.

Authors: Avery JL Berman, Erin L Mazerolle, M Ethan MacDonald, Nicholas P Blockley, Wen-Ming Luh, G Bruce Pike
Conference: nternational Society of Magnetic Resonance in Medicine
Publication date: 2017/4
Gas-free calibration is an appealing new alternative for calibrated fMRI. Using simulations, we determined that estimates of the calibration parameter, M, obtained directly by estimating R2’ with asymmetric spin echo imaging, are negatively biased. This is due to imperfect spin echo refocusing of spins diffusing in the extravascular space. When we modelled the spin echo attenuation as a quadratic-exponential decay, the imperfect refocusing effects were accurately accounted for over intermediate to large vessel sizes. When tested in vivo, increases in M were observed when using the quadratic model, however, additional sources of decay also contributed to M.

Authors: Hongfu Sun, Yuhan Ma, M Ethan MacDonald, G Bruce Pike
Journal: International Society of Magnetic Resonance in Medicine
Publication date: 2017/4
A background field removal step is usually required before the actual inversion. However, it is problematic near the edge of the brain. Single-step QSM methods have been proposed by combining the background field removal with inversion. However, it still erodes the brain edge. A recent study proposed a total field inversion method using R2* map as a preconditioner to boost the convergence speed. Here we propose an inversion method that also performs direct deconvolution on the total field map by adding a Tikhonov regularization to aid the more ill-posed inversion, in addition to the traditional TV regularization.

Authors: M Ethan MacDonald, Parviz Dolati, Alim P Mitha, John H Wong, Richard Frayne
Journal: Magnetic Resonance Imaging
Publication date: 2016/11/1
Publisher: Elsevier
Purpose To explore phase contrast (PC) magnetic resonance imaging of aneurysms and arteriovenous malformations (AVM). PC imaging obtains a vector field of the velocity and can yield additional hemodynamic information, including: volume flow rate (VFR) and intravascular pressure. We expect to find lower VFR distal to aneurysms and higher VFR in vessels of the AVM. Materials and Methods Five cerebral aneurysm and three AVM patients were imaged with PC techniques and compared to VFR of a healthy cohort. VFR was calculated in vessel segments in each patient and compared statistically to the healthy cohort by computing the z-score. Intravascular pressure was calculated in the aneurysms and in the nidus of each AVM. Results We found that patients with aneurysm had z < −0.48 in vessels distal to the aneurysm (reduced flow), while AVM patients had z> 6 in some vessels supplying and draining the nidus (increased flow). Pressures in aneurysms were highly variable between subjects and location, while in the nidus of the AVM patients; pressure trended higher in larger AVMs. Conclusion The study findings confirm the expectation of lower distal flow in aneurysm and higher arterial and venous flow in AVM patients.

Authors: M Ethan MacDonald, Avery JL Berman, Erin L Mazerolle, Rebecca J Williams, G Bruce Pike
Conference: International Society of Magnetic Resonance In Medicine
Publication date: 2016/5
In this work we demonstrate the use of BOLD-fMRI during hyperoxia to obtain perfusion parameters, including CBF, CBV, and MTT. During BOLD imaging, subjects breathing from a respiratory circuit inhaled air whose oxygen content was increased from 21% to 70%. The exhaled oxygen concentration was processed to obtain an arterial input function, and the concentration of bound oxygen in the venous blood was determined by modeling the BOLD time series. Through deconvolution modeling we were able to obtain measurements of CBF, venous CBV, and MTT within expected ranges.

Authors: M Ethan MacDonald, Nils D Forkert, G Bruce Pike, Richard Frayne
Journal: PLoS One
Publication date: 2016/2/24
Publisher: Public Library of Science
Purpose Volume flow rate (VFR) measurements based on phase contrast (PC)-magnetic resonance (MR) imaging datasets have spatially varying bias due to eddy current induced phase errors. The purpose of this study was to assess the impact of phase errors in time averaged PC-MR imaging of the cerebral vasculature and explore the effects of three common correction schemes (local bias correction (LBC), local polynomial correction (LPC), and whole brain polynomial correction (WBPC)). Methods Measurements of the eddy current induced phase error from a static phantom were first obtained. In thirty healthy human subjects, the methods were then assessed in background tissue to determine if local phase offsets could be removed. Finally, the techniques were used to correct VFR measurements in cerebral vessels and compared statistically. Results In the phantom, phase error was measured to be < 2.1 ml/s per pixel and the bias was reduced with the correction schemes. In background tissue, the bias was significantly reduced, by 65.6% (LBC), 58.4% (LPC) and 47.7% (WBPC) (p < 0.001 across all schemes). Correction did not lead to significantly different VFR measurements in the vessels (p=0.997). In the vessel measurements, the three correction schemes led to flow measurement differences of -0.04 ± 0.05 ml/s, 0.09 ± 0.16 ml/s, and -0.02 ± 0.06 ml/s. Although there was an improvement in background measurements with correction, there was no statistical difference between the three correction schemes (p=0.242 in background and p=0.738 in vessels). Conclusions While eddy current induced phase errors can vary between hardware and sequence configurations, our results showed that the impact is small in a typical brain PC-MR protocol and does not have a significant effect on VFR measurements in cerebral vessels.

Authors: Hongfu Sun, M Ethan MacDonald, G Bruce Pike
Journal: Int. Soc. Magn. Res. Med. Scientific Meeting
Publication date: 2016
A method to remove phase offsets in bipolar gradient-echo readouts is proposed. Their effects on Quantitative Susceptibility Mapping (QSM) reconstruction are demonstrated by comparing QSM before and after phase offsets removal.

Authors: Matthew Ethan MacDonald, Richard Frayne
Journal: NMR in Biomedicine
Publication date: 2015/7
Cerebrovascular imaging is of great interest in the understanding of neurological disease. MRI is a non-invasive technology that can visualize and provide information on: (i) the structure of major blood vessels; (ii) the blood flow velocity in these vessels; and (iii) the microcirculation, including the assessment of brain perfusion. Although other medical imaging modalities can also interrogate the cerebrovascular system, MR provides a comprehensive assessment, as it can acquire many different structural and functional image contrasts whilst maintaining a high level of patient comfort and acceptance. The extent of examination is limited only by the practicalities of patient tolerance or clinical scheduling limitations. Currently, MRI methods can provide a range of metrics related to the cerebral vasculature, including: (i) major vessel anatomy via time-of-flight and contrast-enhanced imaging; (ii) blood flow velocity via phase contrast imaging; (iii) major vessel anatomy and tissue perfusion via arterial spin labeling and dynamic bolus passage approaches; and (iv) venography via susceptibility-based imaging. When designing an MRI protocol for patients with suspected cerebral vascular abnormalities, it is appropriate to have a complete understanding of when to use each of the available techniques in the ‘MR angiography toolkit’. In this review article, we: (i) overview the relevant anatomy, common pathologies and alternative imaging modalities; (ii) describe the physical principles and implementations of the above listed methods; (iii) provide guidance on the selection of acquisition parameters; and (iv) describe the existing and potential applications of MRI to the cerebral vasculature and diseases. The focus of this review is on obtaining an understanding through the application of advanced MRI methodology of both normal and abnormal blood flow in the cerebrovascular arteries, capillaries and veins.

Authors: M Ethan MacDonald, Nils D Forkert, G Bruce Pike, Richard Frayne
Conference: Organization of Human Brain Mapping
Publication date: 2015/6

Authors: Matthew Ethan MacDonald, Richard Frayne
Journal: Physiological Measurement
Publication date: 2015/5/28
Publisher: IOP Publishing
Phase contrast (PC) magnetic resonance imaging was used to obtain velocity measurements in 30 healthy subjects to provide an assessment of hemodynamic parameters in cerebral vessels. We expect a lower coefficient-of-variation (COV) of the volume flow rate (VFR) compared to peak velocity (vpeak) measurements and the COV to increase in smaller caliber arteries compared to large arteries. PC velocity maps were processed to calculate vpeak and VFR in 26 vessel segments. The mean, standard deviation and COV, of vpeak and VFR in each segment were calculated. A bootstrap-style analysis was used to determine the minimum number of subjects required to accurately represent the population. Significance of vpeak and VFR asymmetry was assessed in 10 vessel pairs. The bootstrap analysis suggested that averaging more than 20 subjects would give consistent results. When averaged over the subjects, vpeak and VFR ranged from 5.2 ± 7.1 cm s−1, 0.41 ± 0.58 ml s−1 (in the anterior communicating artery; mean ± standard deviation) to 73 ± 23 cm s−1, 7.6 ± 1.7 ml s−1 (in the left internal carotid artery), respectively. A tendency for VFR to be higher in the left hemisphere was observed in 88.8% of artery pairs, while the VFR in the right transverse sinus was larger. The VFR COV was larger than vpeak COV in 57.7% of segments, while smaller vessels had higher COV. Significance and potential impact: VFR COV was not generally higher than vpeak COV. COV was higher in smaller vessels as expected. These summarized values provide a base against which vpeak and VFR in various disease states can be compared.

Authors: M Ethan MacDonald, Avery Berman, Rebecca J Williams, Erin L Mazerolle, G Bruce Pike
Journal: Proc. Intl. Soc. Mag. Reson. Med
Publication date: 2015
In this work, we use a quantitative susceptibility technique calculated from the phase data from BOLD-fMRI. Measurements of the susceptibility time course (BOLD-QSM) are compared to BOLD-fMRI in visual and motor regions. Subjects heads are moved and imaging is repeated. Contrast to noise ratio is calculated in the signals from both techniques and found to be comparable. Five of eight measured signals showed higher CNR with the BOLD-QSM method. A good level of correlation is obtained between the two methods.

Authors: Matthew Ethan MacDonald, Parviz Dolati, Alim P. Mitha, Alim P. Eesa, John H. Wong, Richard Frayne
Journal: Radiology Case Reports
Publication date: 2015
Publisher: Elsevier
Many risk factors have been proposed in the development of the cerebral aneurysms. Hemodynamics including blood velocity, volume flow rate (VFR), and intravascular pressure are thought to be prognostic indicators of aneurysm development. We hypothesize that treatment of cerebral aneurysm using a flow-diverting stent will bring these hemodynamic parameters closer to those observed on the contralateral side. In the current study, a patient with a giant cerebral aneurysm was studied pre- and postoperatively using phase contrast MRI (PC-MRI) to measure the hemodynamic changes resulting from the deployment of a flow-diverting stent. PC-MRI was used to calculate intravascular pressure, which was compared to more invasive endovascular catheter-derived measurements. After stent placement, the measured VFRs in vessels of the treated hemisphere approached those measured on the contralateral side, and flow symmetry changed from a laterality index of -0.153 to 0.116 in the middle cerebral artery. Pressure estimates derived from the PC-MRI velocity data had an average difference of 6.1% as compared to invasive catheter transducer measurements. PC-MRI can measure the hemodynamic parameters with the same accuracy as invasive methods pre- and postoperatively.

Authors: Matthew Ethan MacDonald
Publication date: 2014/9/19
Publisher: Graduate Studies
This thesis explores quantitative cerebrovascular magnetic resonance (MR) imaging, a broad topic, with the aim of providing relevant numerical values associated with blood flow through the brain. Anatomy, pathology and basic angiography methods were reviewed. Several other MR imaging methods for obtaining cerebrovascular measurements are reviewed. Exploration of the lowest achievable variance with MR imaging was undertaken through simulation using a digital brain phantom. A phantom was constructed from a healthy human brain data set using advanced methodologies to yield volumes of MR parameters (i.e., coil sensitivity, B0, B1, M0, T1, T2, T2*, and magnetic susceptibility). The digital brain phantom was then used to simulate the MR acquisition process and generate images, in order to determine the minimal achievable variance as a function of coil profile distortion. It was found that the degree of coil correlation could affect the lowest achievable variance by up to 2× to 3× over practical ranges. The focus of the experimental chapters is on phase contrast velocity mapping and metrics that can be derived from velocity maps, such as: peak velocity, volume flow rate, and intravascular pressure. Prospective imaging was performed on healthy humans, and eight patients (five cerebral aneurysms and three arteriovenous malformations). A case study of a giant cerebral aneurysm was explored in greater detail, and stent treatment was shown to reduce flow asymmetry. Peak velocity and volume flow rate was determined for vessels in the normal brain. Bootstrapping is performed to assert that group-wise measurements are representative of the broader population and flow laterality is examined. Significant flow asymmetry was found between several paired vessel segments. Flow in the patients was imaged, and derived metrics were compared to the healthy cohort. Patients with aneurysm were found to have significantly lower flow in vessels distal to the aneurysm, while arteriovenious malformation patients were found to have significantly higher flow in vessels supplying the nidus.

Authors: M Ethan MacDonald, M Louis Lauzon, Richard Frayne
Conference: International Society of Magnetic Resonance in Medicine
Publication date: 2014/5
In this work combined methodologies for rapidly acquiring parametric maps of the brain are described. Several parameters in the brain, including: T1, T2, T2*, magnetic susceptibility and proton density are calculated, in addition to several machine distortion parameters, including: B0 and B1 field inhomogeneity, and coil profiles. The protocol time used to produce these images was less than 26 minutes, and resulted in whole brain coverage with 1 mm^3 isotropic resolution. Collection of these key physiological and machine distortion parameters will allow for advanced simulation of the MR system.

Authors: M Ethan MacDonald, M Louis Lauzon, Richard Frayne
Conference: International Society of Magnetic Resonance in Medicine
Publication date: 2014/5
To quantify MR parameters of the brain in a timely fashion. Target parameters include: B0 and B1 field Matrix Size inhomogeneity, coil sensitivity profiles, T1, T2, T2*, net Factor magnetization (M0), and magnetic susceptibility. Whole brain coverage was achieved with 1 mm isotropic resolution in a scan time of < 26 minutes.

Authors: M Ethan MacDonald, Estee Lee, Ting Lee, Jordan Woehr, Chris d'Esterre, Michael R Smith, Richard Frayne
Journal: Proc. Intl. Soc. Mag. Reson. Med
Publication date: 2014
In this work we use dynamic susceptibility contrast MR imaging and fit a duel compartmental model to the residue function. The proposed duel compartmental model has been used in CT perfusion with great success, consisting of a rectangular function and exponential decay. The model is interactively fit to the residue function with an iterative least squares conjugate gradient algorithm. Parametric maps and goodness of fit maps were produced for an acute ischemic stroke patient. Fit quality is high in regions of normal flow, but where flow is low, < 10 ml/100 g/min, the quality of the fit is diminished.

Authors: M Ethan MacDonald, Parviz Dolati, John H Wong, Richard Frayne
Journal: Proc. Intl. Soc. Mag. Reson. Med
Publication date: 2014
Phase contrast (PC) magnetic resonance (MR) imaging can be used to obtain maps of flow velocity. Hemodynamic parameters such as peak velocity (vpeak) and volume flow rate (VFR) can be derived from from these velocity maps. Blood flow through the brain is known to be highly variable between subjects and even in repeated measurements of the same subject. Velocity mapping techniques have had limited clinical utility because knowledge of normal flow measurements is poorly characterized. PC-MR can be acquired in 3D or 4D, higher spatial resolution is achievable with 3D imaging. This work aims to establish vpeak and VFR in a broader range of cerebral vessels than in previous studies. VFR is known to be affected by partial volume errors, resulting in an overestimation.

Journal: Canadian Journal of surgery. Journal Canadien de Chirurgie
Publication date: 2013/12/1
The risk of endoleak after infrarenal endovascular aortic aneurysm repair is significant and thus patients require lifelong imaging surveillance. This surveillance comes with its own set of risks associated with radiation exposure and contrast dye use, as well as increased costs. We sought to determine the predictive value of a negative first postoperative imaging study on the long-term risk of developing an endoleak in a varied tertiary care vascular practice. We sought to determine if there are characteristics that might lend a subgroup of patients to be able to follow less rigorous imaging protocols.

Authors: E Lee, M MacDonald, R Frayne
Conference: Stroke
Publication date: 2013/12/1
Publisher: LIPPINCOTT WILLIAMS & WILKINS

Authors: M Ethan MacDonald, R Marc Lebel, Richard Frayne
Conference: International Society of Magnetic Resonance in Medicine
Publication date: 2013/4
In this work we demonstrate L1 constrained reconstruction of a variable density under sampled series, a similar method has been demonstrated for dynamic susceptibility contrast bolus chase imaging. Using the positive contrast of gadolinium in an endovascular catheter we show 3D catheter tracking with high temporal (4.7 Hz) and spatial resolution (64x64x16 acquisition matrix). An acceleration rate of 12.2x is achieved with the constrained reconstruction while maintaining good catheter conspicuity. Maximum intensity projections and 3D iso surfaces are used for rendering catheter images.

Authors: Estee Lee, M Ethan MacDonald, Richard Frayne
Conference: Magnetic Resonance Angiography Club
Publication date: 2013/4
DCE MR imaging provides a linear relationship between signal intensity and [contrast agent (Gd-DTPA)]. Clinically useful perfusion information can be derived (i.e., CBF, CBV, etc.).

Authors: ME MacDonald, B Menon, P Dolati, M Goyal, R Frayne
Conference: Stroke
Publication date: 2012/11/1
Publisher: LIPPINCOTT WILLIAMS & WILKINS
Ischemic stroke is a reduction of cerebral blood flow (CBF) to a region of brain tissue

Authors: ME MacDonald, N Swailies, MR Smith, JN Nielsen, R Frayne
Conference: Accelerated Magnetic Resonance Imaging 3rd International Workshop, Freiburg, Germany
Publication date: 2012/9
The Cramer Rao Lower Bound (CRLB) represents the smallest variance achievable for an unbiased estimator. The estimator that meets the CRLB is called the minimum variance unbiased (MVU) estimator. When reconstructing magnitude images from magnetic resonance (MR) k-space, the MVU image estimator is found to be the Fourier transform in the fully sampled case [1]. By using a Bayesian approach, i.e., a biased reconstruction, such as many of the proposed constrained sensing reconstructions [2-4] then a lower image mean square error (MSE) may be achievable over a certain range of parameters [5]. Several MR imaging methods require phase images, including: phase contrast velocity encoding, susceptibility-weighted imaging, B0-field mapping and quantitative susceptibility mapping. The probability density function for noise in phase images is known to be quite different than in magnitude images. It is our hypothesis that the Bayesian constrained reconstruction will perform better at producing phase images than the MVU over a range of acceleration factors. In this work we perform numeric simulations on real data, obtained by imaging a custom imaging phantom and a human brain, to demonstrate variation in the image phase MSE with respect to acceleration factor.

Authors: S Beladi, CR McCreary, EE Smith, ML Lauzon, ME MacDonald, R Frayne
Conference: 20th ISMRM Scientific Meeting, At Melbourne, Australia
Publication date: 2012/5
This study evaluates the diagnostic values of susceptibility weighted imaging (SWI) and quantitative susceptibility mapping (QSM) for cerebral microbleed (CMB) detection in CAA patients. The QSM technique was implemented using L1-norm nonlinear regularization to accurately estimate the iron (hemosiderin) quantity in CMBs. A radiologist resident detected the QSMs and region of interest (ROI) study was performed on eighty randomly selected ROIs, containing a CMB and some surrounding normal tissue. According to the statistical results, QSM was proposed as an improved approach, which results in higher signal change between CMB and the surrounding tissue, reveals the actual size of the CMBs and provides quantitative measures that are independent of the imaging parameters.

Authors: Matthew Ethan MacDonald, Parviz Dolati, Linda B Andersen, Richard Frayne
Conference: 20th ISMRM Scientific Meeting, At Melbourne, Australia
Publication date: 2012/5
Ischemic stroke occurs when blood vessels feeding the brain become occluded and tissues do not receive adequate nutrition. Function is initially impaired, and with time, if flow is not restored the tissue will eventually become infarcted. Validation of restored flow is confirmed clinically by evaluating the macroscopic blood vessels with x-ray imaging using digital subtraction angiography (DSA) or with computed tomography (CT) angiography [1]. There can be a disconnection between restored flow observed with DSA and patient outcomes, as DSA does not provide information about the microscopic blood flow (i.e., it does not provide information about the capillary bed and tissue perfusion). Measures of tissue perfusion can be obtained by kinetic modeling of contrast agent passage imaged rapidly with CT [2] or magnetic resonance (MR) imaging [3,4], and with arterial spin labeling (ASL) MR imaging [5]; of these three methods, ASL allows for the fastest repeatable measurements. It is our hypothesis that perfusion can be measured transiently with ASL during neurovascular interventions leading to an improved understanding of flow restoration, and that there will be a detectable difference on ASL perfusion during carotid occlusion. In this study we simulated an occlusion in a canine model with endovascular devices and then analyzed the difference of perfusion between different vascular territories.

Authors: Matthew Ethan MacDonald, David Adair, Parviz Dolati, Richard Frayne
Conference: 20th ISMRM Scientific Meeting, At Melbourne, Australia
Publication date: 2012/5
Real-time magnetic resonance (MR) imaging has been proposed as a method for device tracking and visualization by several research groups [1-3]. MR imaging has several advantages over the gold standard X-ray imaging, including: 1) Superior contrast between soft tissues, 2) potential for oblique 3D imaging, and 3) absence of ionizing radiation. Challenges with real-time MR imaging include design of fast acquisitions and efficient processing, which has led to most real-time MR implementations to be strictly 2D, or bi-planar rather than 3D. Several new methods have been proposed for reducing image acquisition time through undersampling, and in addition reconstruct images from the undersampled data. Many modern reconstructions are non-linear and thus very computationally intensive and do not lend well for real-time applications. Undersampling which creates incoherent aliasing can be performed at the penalty of increased apparent noise in images, and with compressed sensing type reconstructions, this noise level can be reduced but at the expense of computational demand [5]. It is our hypothesis that we can perform fast imaging with random undersampling to visualize contrast inflow and gadolinium filled catheters at a higher frame rate. In this study we designed a hardware configuration and software application for fast MR image reconstruction and viewed the result on the MR console. We then timed the application imaging reconstructions at various volume sizes and report the results. Random undersampling trajectories that result in incoherent aliasing are used to accelerate the 3D acquisition by factors of 2× and 4×, but only a linear transform (fast Fourier transform) is used for reconstruction to maintain low latency.

Authors: Matthew Ethan MacDonald, LB Anderson, CR McCreary, Richard Frayne
Conference: 23rd Annual International Magnetic Resonance Angiography Club Meeting
Publication date: 2011/6

Authors: MR Smith, ME MacDonald, E Marasco, M Salluzzi, P Gauderon, R Frayne
Conference: 23rd Annual International Magnetic Resonance Angiography Club Meeting
Publication date: 2011/6
With the availability of efficient algorithms for non-linear optimizations there has been an explosion of interest in applying compressive sensing (CS) techniques [1, 2]. A key idea behind MR sparse angiography is the gathering of reduced k-space data sets. This concept traces back to super-resolution reconstruction (SR) algorithms [3, 4] designed to improve upon techniques of earlier partial Fourier transform reconstructions [5]. We discuss some of the processes and validation techniques from super-resolution reconstruction that can be adapted to compressed sensing reconstruction.

Authors: Matthew Ethan MacDonald, Micheal Richard Smith, Richard Frayne
Conference: International Society of Magnetic Resonance in Medicine
Publication date: 2011/5
Dynamic susceptibility contrast (DSC) MR imaging can be used to determine the perfusion state of brain tissue during acute ischemic stroke. Perfusion-weighted imaging (PWI) when combined with diffusion-weighted imaging (DWI) has been proposed as a method for determining the volume of salvageable tissue during initial hours of onset (< 6 h) [1]. Use of the cerebral blood flow (CBF) esti- mates obtained from PWI is effective at identifying ischemic tissue, however, the accuracy of this parameter has been observed to vary in performance with the type of deconvolution technique used for its calculation [2]. Several deconvolution methods have been observed to have an MTT dependence due to regularization, resulting in an underestimation of CBF values in healthy tissues (i.e., healthy tissues have shorter mean-transit times (MTT) and are more heavily filtered, while ischemic tissue has longer MTT and less signal removed) [3]. We hypothesize that by restoring high-frequency components during the deconvolution process, there will be an improvement observed in the CBF accuracy and in image contrast between healthy and ischemic regions, resulting in better detection of final infarct.

Authors: ME MacDonald, N Swailes, LB Andersen, CM McCreary, R Frayne
Conference: 19th ISMRM
Publication date: 2011/5

Authors: Armin Eilaghi, D Adam McLean, David G Gobbi, M Ethan MacDonald, M Louis Lauzon, Marina Salluzzi, Richard Frayne
Journal: NeuroImage
Publication date: 2011
Magnetic susceptibility changes due to iron deposition in deep brain nuclei are an important characteristic of aging.[1] Iron is deposited in the brain via a number of mechanisms including leakage of blood from the vascular system. Iron deposition is expected in both neurodegeneration [2] and normal aging.[3] The spatial and temporal variation of iron deposits can be identified and measured using quantitative susceptibility mapping (QSM).[2] In this study, we use QSM to quantify susceptibility changes in the external and internal globus pallidus (GP), putamen, caudate nucleus (CN) and red nucleus (RN); five regions that have been previously suggested to have iron changes due to aging.[3] Specifically, we compare quantitative susceptibility values between groups of young and elderly, cognitively normal subjects.

Authors: R B Stafford, M E MacDonald, R Frayne
Conference: 18th ISMRM
Publication date: 2010/4
Gradient warp correction is computationally intensive, and therefore not always practical for real-time imaging [1-3]. For real-time MR applications, such as MR-guided endovascular therapy, gradient warping can reduce geometric fidelity, preventing accurate visual feedback to an interventionalist. OpenGL (Open Graphics Language) is a graphics display library with mathematical graphics functions called non-uniform rational B-splines (NURBS) that can project a 2D texture onto a 3D surface within the fast display framework [4]. Our hypothesis is that OpenGL NURBS surfaces can be used for fast, real-time gradient warp correction.

Authors: M E MacDonald, R B Stafford, M L Lauzon, R Frayne
Conference: 18th ISMRM
Publication date: 2010/4
Fast imaging applications require high frame rates and low latency, thus the choice of image acquisition parameters and image reconstruction algorithms is crucial. For example, reducing the number of phase-encodings reduces overall scan time, but reduces spatial resolution. Furthermore, algorithms for gradient warp correction are cumbersome for real-time image reconstruction.1 We propose a new strategy that utilizes a calibration scan2 to produce gradient warp corrected images from vastly undersampled data. Unlike parallel imaging, this technique uses only a single coil. Our hypothesis is that the Gradient warp and UnderSampled Transform Operator (GUSTO) algorithm can produce images in real time with an increased frame rate while preserving good geometric fidelity.

Authors: ME MacDonald, RB Stafford, R Frayne
Journal: Medical Physics
Publication date: 2009/9/1
Publisher: American Association of Physicists in Medicine
Angioplasty has been demonstrated as an effective treatment for cardiovascular diseases such as carotid stenosis, having similar patient outcomes to the once dominant endarectomy technique. Angioplasty is an attractive choice, as it is much less invasive. However, angioplasty procedures are hinged on the guidance of catheters through the vascular system, and imaging is required for this process. X-ray is almost always used for these types of interventions, but has several noted drawbacks, including the exposure of ionizing radiation to both patients and staff. Magnetic resonance (MR) imaging has been used in previous experiments at different centres and overcomes some of the problems associated with X-ray imaging. Here, we propose a real-time imaging system, for use in catheter guiding applications, and look at parameters and techniques that will increase the overall frame rate displayed to an in-room monitor. By modifying a fast gradient recalled echo (FGRE) sequence, and ported data directly to an image reconstruction station, implemented on an iMac computer, images are reconstructed and display in real time. By using algorithms such as variable rate k-space acquisition (varking), multi-phase array coils, reducing the number of phase-encode lines, and reducing the analog to digital converter (ADC) sampling rate, frame rate was improved from ∼1 Hz to ∼5Hz. Analysis of images, pre- and post-optimization, yield comparable quality by inspection, and an improved SNR from 45 to 160. This system has been designed to perform MR angioplasty procedures, which will the next step in our research project using animal models.

Authors: M Ethan MacDonald, Richard Frayne, Michael R Smith
Journal: CMBES Proceedings
Publication date: 2009/5/20
The quantification of cerebral blood flow (CBF) in patients suffering from ischemic stroke will likely become a key clinical tool for assessing their prognosis. By its very definition, ischemic stroke represents a reduction of blood flow (ischemia) to a region of brain tissue, most commonly due to a blocked vessel. Magnetic resonance (MR) perfusion imaging can provide estimates of CBF by monitoring the passage of a gadolinium-based contrast agent as it travels through the cerebral vascular system over time.[1, 2] During contrast passage, images are gathered every 1 s to 2 s over a period of 60 s to 90 s. From these images a signal intensity time series can be constructed for each image voxel.