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Improved Task-based Functional MRI Language Mapping in Patients with Brain Tumors through Marchenko-Pastur Principal Component Analysis Denoising

Ades-Aron, Benjamin; Lemberskiy, Gregory; Veraart, Jelle; Golfinos, John; Fieremans, Els; Novikov, Dmitry S; Shepherd, Timothy
Background Functional MRI improves preoperative planning in patients with brain tumors, but task-correlated signal intensity changes are only 2%-3% above baseline. This makes accurate functional mapping challenging. Marchenko-Pastur principal component analysis (MP-PCA) provides a novel strategy to separate functional MRI signal from noise without requiring user input or prior data representation. Purpose To determine whether MP-PCA denoising improves activation magnitude for task-based functional MRI language mapping in patients with brain tumors. Materials and Methods In this Health Insurance Portability and Accountability Act-compliant study, MP-PCA performance was first evaluated by using simulated functional MRI data with a known ground truth. Right-handed, left-language-dominant patients with brain tumors who successfully performed verb generation, sentence completion, and finger tapping functional MRI tasks were retrospectively identified between January 2017 and August 2018. On the group level, for each task, histograms of z scores for original and MP-PCA denoised data were extracted from relevant regions and contralateral homologs were seeded by a neuroradiologist blinded to functional MRI findings. Z scores were compared with paired two-sided t tests, and distributions were compared with effect size measurements and the Kolmogorov-Smirnov test. The number of voxels with a z score greater than 3 was used to measure task sensitivity relative to task duration. Results Twenty-three patients (mean age ± standard deviation, 43 years ± 18; 13 women) were evaluated. MP-PCA denoising led to a higher median z score of task-based functional MRI voxel activation in left hemisphere cortical regions for verb generation (from 3.8 ± 1.0 to 4.5 ± 1.4; P < .001), sentence completion (from 3.7 ± 1.0 to 4.3 ± 1.4; P < .001), and finger tapping (from 6.9 ± 2.4 to 7.9 ± 2.9; P < .001). Median z scores did not improve in contralateral homolog regions for verb generation (from -2.7 ± 0.54 to -2.5 ± 0.40; P = .90), sentence completion (from -2.3 ± 0.21 to -2.4 ± 0.37; P = .39), or finger tapping (from -2.3 ± 1.20 to -2.7 ± 1.40; P = .07). Individual functional MRI task durations could be truncated by at least 40% after MP-PCA without degradation of clinically relevant correlations between functional cortex and functional MRI tasks. Conclusion Denoising with Marchenko-Pastur principal component analysis led to higher task correlations in relevant cortical regions during functional MRI language mapping in patients with brain tumors. © RSNA, 2020 Online supplemental material is available for this article.
PMID: 33289611
ISSN: 1527-1315
CID: 4708782

Approximating anatomically-guided PET reconstruction in image space using a convolutional neural network

Schramm, Georg; Rigie, David; Vahle, Thomas; Rezaei, Ahmadreza; Van Laere, Koen; Shepherd, Timothy; Nuyts, Johan; Boada, Fernando
In the last two decades, it has been shown that anatomically-guided PET reconstruction can lead to improved bias-noise characteristics in brain PET imaging. However, despite promising results in simulations and first studies, anatomically-guided PET reconstructions are not yet available for use in routine clinical because of several reasons. In light of this, we investigate whether the improvements of anatomically-guided PET reconstruction methods can be achieved entirely in the image domain with a convolutional neural network (CNN). An entirely image-based CNN post-reconstruction approach has the advantage that no access to PET raw data is needed and, moreover, that the prediction times of trained CNNs are extremely fast on state of the art GPUs which will substantially facilitate the evaluation, fine-tuning and application of anatomically-guided PET reconstruction in real-world clinical settings. In this work, we demonstrate that anatomically-guided PET reconstruction using the asymmetric Bowsher prior can be well-approximated by a purely shift-invariant convolutional neural network in image space allowing the generation of anatomically-guided PET images in almost real-time. We show that by applying dedicated data augmentation techniques in the training phase, in which 16 [18F]FDG and 10 [18F]PE2I data sets were used, lead to a CNN that is robust against the used PET tracer, the noise level of the input PET images and the input MRI contrast. A detailed analysis of our CNN in 36 [18F]FDG, 18 [18F]PE2I, and 7 [18F]FET test data sets demonstrates that the image quality of our trained CNN is very close to the one of the target reconstructions in terms of regional mean recovery and regional structural similarity.
PMID: 32971267
ISSN: 1095-9572
CID: 4624682

MR Susceptibility Imaging with a Short TE (MR-SISET): A Clinically Feasible Technique to Resolve Thalamic Nuclei

Chung, S; Storey, P; Shepherd, T M; Lui, Y W
The thalamus consists of several functionally distinct nuclei, some of which serve as targets for functional neurosurgery. Visualization of such nuclei is a major challenge due to their low signal contrast on conventional imaging. We introduce MR susceptibility imaging with a short TE, leveraging susceptibility differences among thalamic nuclei, to automatically delineate 15 thalamic subregions. The technique has the potential to enable direct targeting of thalamic nuclei for functional neurosurgical guidance.
PMID: 32675340
ISSN: 1936-959x
CID: 4529162

Diffusion MRI biomarkers of white matter microstructure vary nonmonotonically with increasing cerebral amyloid deposition

Dong, Jian W; Jelescu, Ileana O; Ades-Aron, Benjamin; Novikov, Dmitry S; Friedman, Kent; Babb, James S; Osorio, Ricardo S; Galvin, James E; Shepherd, Timothy M; Fieremans, Els
Beta amyloid (Aβ) accumulation is the earliest pathological marker of Alzheimer's disease (AD), but early AD pathology also affects white matter (WM) integrity. We performed a cross-sectional study including 44 subjects (23 healthy controls and 21 mild cognitive impairment or early AD patients) who underwent simultaneous PET-MR using 18F-Florbetapir, and were categorized into 3 groups based on Aβ burden: Aβ- [mean mSUVr ≤1.00], Aβi [1.00 < mSUVr <1.17], Aβ+ [mSUVr ≥1.17]. Intergroup comparisons of diffusion MRI metrics revealed significant differences across multiple WM tracts. Aβi group displayed more restricted diffusion (higher fractional anisotropy, radial kurtosis, axonal water fraction, and lower radial diffusivity) than both Aβ- and Aβ+ groups. This nonmonotonic trend was confirmed by significant continuous correlations between mSUVr and diffusion metrics going in opposite direction for 2 cohorts: pooled Aβ-/Aβi and pooled Aβi/Aβ+. The transient period of increased diffusion restriction may be due to inflammation that accompanies rising Aβ burden. In the later stages of Aβ accumulation, neurodegeneration is the predominant factor affecting diffusion.
PMID: 32111392
ISSN: 1558-1497
CID: 4324492

Direct In Vivo MRI Discrimination of Brain Stem Nuclei and Pathways

Shepherd, T M; Ades-Aron, B; Bruno, M; Schambra, H M; Hoch, M J
BACKGROUND AND PURPOSE/OBJECTIVE:The brain stem is a complex configuration of small nuclei and pathways for motor, sensory, and autonomic control that are essential for life, yet internal brain stem anatomy is difficult to characterize in living subjects. We hypothesized that the 3D fast gray matter acquisition T1 inversion recovery sequence, which uses a short inversion time to suppress signal from white matter, could improve contrast resolution of brain stem pathways and nuclei with 3T MR imaging. MATERIALS AND METHODS/METHODS:-space to reduce motion; total scan time = 58 minutes). One subject returned for an additional 5-average study that was combined with a previous session to create a highest quality atlas for anatomic assignments. A 1-mm isotropic resolution, 12-minute version, proved successful in a patient with a prior infarct. RESULTS:The fast gray matter acquisition T1 inversion recovery sequence generated excellent contrast resolution of small brain stem pathways in all 3 planes for all 10 subjects. Several nuclei could be resolved directly by image contrast alone or indirectly located due to bordering visualized structures (eg, locus coeruleus and pedunculopontine nucleus). CONCLUSIONS:The fast gray matter acquisition T1 inversion recovery sequence has the potential to provide imaging correlates to clinical conditions that affect the brain stem, improve neurosurgical navigation, validate diffusion tractography of the brain stem, and generate a 3D atlas for automatic parcellation of specific brain stem structures.
PMID: 32354712
ISSN: 1936-959x
CID: 4438632

Multi-parametric quantitative in vivo spinal cord MRI with unified signal readout and image denoising

Grussu, Francesco; Battiston, Marco; Veraart, Jelle; Schneider, Torben; Cohen-Adad, Julien; Shepherd, Timothy M; Alexander, Daniel C; Fieremans, Els; Novikov, Dmitry S; Gandini Wheeler-Kingshott, Claudia A M
Multi-parametric quantitative MRI (qMRI) of the spinal cord is a promising non-invasive tool to probe early microstructural damage in neurological disorders. It is usually performed in vivo by combining acquisitions with multiple signal readouts, which exhibit different thermal noise levels, geometrical distortions and susceptibility to physiological noise. This ultimately hinders joint multi-contrast modelling and makes the geometric correspondence of parametric maps challenging. We propose an approach to overcome these limitations, by implementing state-of-the-art microstructural MRI of the spinal cord with a unified signal readout in vivo (i.e. with matched spatial encoding parameters across a range of imaging contrasts). We base our acquisition on single-shot echo planar imaging with reduced field-of-view, and obtain data from two different vendors (vendor 1: Philips Achieva; vendor 2: Siemens Prisma). Importantly, the unified acquisition allows us to compare signal and noise across contrasts, thus enabling overall quality enhancement via multi-contrast image denoising methods. As a proof-of-concept, here we provide a demonstration with one such method, known as Marchenko-Pastur (MP) Principal Component Analysis (PCA) denoising. MP-PCA is a singular value (SV) decomposition truncation approach that relies on redundant acquisitions, i.e. such that the number of measurements is large compared to the number of components that are maintained in the truncated SV decomposition. Here we used in vivo and synthetic data to test whether a unified readout enables more efficient MP-PCA denoising of less redundant acquisitions, since these can be denoised jointly with more redundant ones. We demonstrate that a unified readout provides robust multi-parametric maps, including diffusion and kurtosis tensors from diffusion MRI, myelin metrics from two-pool magnetisation transfer, and T1 and T2 from relaxometry. Moreover, we show that MP-PCA improves the quality of our multi-contrast acquisitions, since it reduces the coefficient of variation (i.e. variability) by up to 17% for mean kurtosis, 8% for bound pool fraction (myelin-sensitive), and 13% for T1, while enabling more efficient denoising of modalities limited in redundancy (e.g. relaxometry). In conclusion, multi-parametric spinal cord qMRI with unified readout is feasible and provides robust microstructural metrics with matched resolution and distortions, whose quality benefits from multi-contrast denoising methods such as MP-PCA.
PMID: 32360689
ISSN: 1095-9572
CID: 4429722

Neuropathologic Changes in Sudden Unexplained Death in Childhood

McGuone, Declan; Leitner, Dominique; William, Christopher; Faustin, Arline; Leelatian, Nalin; Reichard, Ross; Shepherd, Timothy M; Snuderl, Matija; Crandall, Laura; Wisniewski, Thomas; Devinsky, Orrin
Sudden unexplained death in childhood (SUDC) affects children >1-year-old whose cause of death remains unexplained following comprehensive case investigation and is often associated with hippocampal abnormalities. We prospectively performed systematic neuropathologic investigation in 20 SUDC cases, including (i) autopsy data and comprehensive ancillary testing, including molecular studies, (ii) ex vivo 3T MRI and extensive histologic brain samples, and (iii) blinded neuropathology review by 2 board-certified neuropathologists. There were 12 girls and 8 boys; median age at death was 33.3 months. Twelve had a history of febrile seizures, 85% died during apparent sleep and 80% in prone position. Molecular testing possibly explained 3 deaths and identified genetic mutations in TNNI3, RYR2, and multiple chromosomal aberrations. Hippocampal abnormalities most often affected the dentate gyrus (altered thickness, irregular configuration, and focal lack of granule cells), and had highest concordance between reviewers. Findings were identified with similar frequencies in cases with and without molecular findings. Number of seizures did not correlate with hippocampal findings. Hippocampal alterations were the most common finding on histological review but were also found in possibly explained deaths. The significance and specificity of hippocampal findings is unclear as they may result from seizures, contribute to seizure pathogenesis, or be an unrelated phenomenon.
PMID: 31995186
ISSN: 1554-6578
CID: 4294212

Brain 18F-FDG-PET: Utility in the Diagnosis of Dementia and Epilepsy

Lotan, Eyal; Friedman, Kent P; Davidson, Tima; Shepherd, Timothy M
BACKGROUND:The authors reviewed the two most common current uses of brain 18F-labeled fluoro-2-deoxyglucose positron emission tomography (FDG-PET) at a large academic medical center. For epilepsy patients considering surgical management, FDG-PET can help localize epileptogenic lesions, discriminate between multiple or discordant EEG or MRI findings, and predict prognosis for post-surgical seizure control. In elderly patients with cognitive impairment, FDG-PET often demonstrates lobar-specific patterns of hypometabolism that suggest particular underlying neurodegenerative pathologies, such as Alzheimer's disease. FDG-PET of the brain can be a key diagnostic modality and contribute to improved patient care.
PMID: 32147984
ISSN: 1565-1088
CID: 4348652

On the Origins of Diffusion MRI Signal Changes in Stroke

Blackband, Stephen J; Flint, Jeremy J; Hansen, Brian; Shepherd, Timothy M; Lee, Choong H; Streit, Wolfgang J; Forder, John R
Magnetic resonance imaging (MRI) is a leading diagnostic technique especially for neurological studies. However, the physical origin of the hyperintense signal seen in MR images of stroke immediately after ischemic onset in the brain has been a matter of debate since it was first demonstrated in 1990. In this article, we hypothesize and provide evidence that changes in the glial cells, comprising roughly one-half of the brain's cells and therefore a significant share of its volume, accompanying ischemia, are the root cause of the MRI signal change. Indeed, a primary function of the glial cells is osmoregulation in order to maintain homeostasis in the neurons and nerve fibers for accurate and consistent function. This realization also impacts our understanding of signal changes in other tissues following ischemia. We anticipate that this paradigm shift will facilitate new and improved models of MRI signals in tissues, which will, in turn, impact clinical utility.
PMCID:7344185
PMID: 32714267
ISSN: 1664-2295
CID: 4539222

Multi -parametric quantitative in vivo spinal cord MRI with unified signal readout and image denoising

Grussu, Francesco; Battiston, Marco; Veraart, Jelle; Schneider, Torben; Cohen-Adad, Julien; Shepherd, Timothy M.; Alexander, Daniel C.; Fieremans, Els; Novikov, Dmitry S.; Wheeler-Kingshott, Claudia A. M. Gandini
ISI:000542370300008
ISSN: 1053-8119
CID: 4525782