Comparison of Dentatorubrothalamic Tractography Methods Based on the Anatomy of the Rubral Wing.

BACKGROUND AND OBJECTIVES: Precise localization of the dentatorubrothalamic (DRT) tract can facilitate anatomic targeting in MRI-guided high-intensity focused ultrasound (HIFU) thalamotomy and thalamic deep brain stimulation for tremor. The anatomic segment of DRT fibers adjacent to the ventral intermediate nucleus of the thalamus (VIM), referred to as the rubral wing (RW), may be directly visualized on the fast gray matter acquisition T1 inversion recovery. We compared reproducibility, lesion overlap, and clinical outcomes when reconstructing the DRT tract using a novel anatomically defined RW region of interest, DRT-RW, to an existing tractography method based on the posterior subthalamic area region of interest (DRT-PSA). METHODS: We reviewed data of 23 patients with either essential tremor (n = 18) or tremor-predominant Parkinson's disease (n = 5) who underwent HIFU thalamotomy, targeting the VIM. DRT tractography, ipsilateral to the lesion, was created based on either DRT-PSA or DRT-RW. Volume sections of each tract were created and dice similarity coefficients were used to measure spatial overlap between the 2 tractographies. Post-HIFU lesion size and location (on postoperative T2 MRI) was correlated with tremor outcomes and side effects for both DRT tractography methods and the RW itself. RESULTS: DRT-PSA passed through the RW and DRT-RW intersected with the ROIs of the DRT-PSA in all 23 cases. A higher percentage of the RW was ablated in patients who achieved tremor control (18.9%, 95% CI 15.1, 22.7) vs those without tremor relief (6.7%, 95% CI% 0, 22.4, P = .017). In patients with tremor control 6 months postoperatively (n = 12), those with side effects (n = 6) had larger percentages of their tracts ablated in comparison with those without side effects in both DRT-PSA (44.8, 95% CI 31.8, 57.8 vs 24.2%, 95% CI 12.4, 36.1, P = .025) and DRT-RW (35.4%, 95% CI 21.5, 49.3 vs 21.7%, 95% CI 12.7, 30.8, P = .030). CONCLUSION: Tractography of the DRT could be reconstructed by direct anatomic visualization of the RW on fast gray matter acquisition T1 inversion recovery-MRI. Anatomic planning is expected to be quicker, more reproducible, and less operator-dependent.

Unconstrained quantitative magnetization transfer imaging: disentangling T1 of the free and semi-solid spin pools.

Since the inception of magnetization transfer (MT) imaging, it has been widely assumed that Henkelman's two spin pools have similar longitudinal relaxation times, which motivated many researchers to constrain them to each other. However, several recent publications reported a T1s of the semi-solid spin pool that is much shorter than T1f of the free pool. While these studies tailored experiments for robust proofs-of-concept, we here aim to quantify the disentangled relaxation processes on a voxel-by-voxel basis in a clinical imaging setting, i.e., with an effective resolution of 1.24mm isotropic and full brain coverage in 12min. To this end, we optimized a hybrid-state pulse sequence for mapping the parameters of an unconstrained MT model. We scanned four people with relapsing-remitting multiple sclerosis (MS) and four healthy controls with this pulse sequence and estimated T1f≈1.84s and T1s≈0.34s in healthy white matter. Our results confirm the reports that T1s≪T1f and we argue that this finding identifies MT as an inherent driver of longitudinal relaxation in brain tissue. Moreover, we estimated a fractional size of the semi-solid spin pool of m0s≈0.212, which is larger than previously assumed. An analysis of T1f in normal-appearing white matter revealed statistically significant differences between individuals with MS and controls.

Rapid quantitative magnetization transfer imaging: Utilizing the hybrid state and the generalized Bloch model.

PURPOSE: To explore efficient encoding schemes for quantitative magnetization transfer (qMT) imaging with few constraints on model parameters. THEORY AND METHODS: We combine two recently proposed models in a Bloch-McConnell equation: the dynamics of the free spin pool are confined to the hybrid state, and the dynamics of the semi-solid spin pool are described by the generalized Bloch model. We numerically optimize the flip angles and durations of a train of radio frequency pulses to enhance the encoding of three qMT parameters while accounting for all eight parameters of the two-pool model. We sparsely sample each time frame along this spin dynamics with a three-dimensional radial koosh-ball trajectory, reconstruct the data with subspace modeling, and fit the qMT model with a neural network for computational efficiency. RESULTS: We extracted qMT parameter maps of the whole brain with an effective resolution of 1.24 mm from a 12.6-min scan. In lesions of multiple sclerosis subjects, we observe a decreased size of the semi-solid spin pool and longer relaxation times, consistent with previous reports. CONCLUSION: The encoding power of the hybrid state, combined with regularized image reconstruction, and the accuracy of the generalized Bloch model provide an excellent basis for efficient quantitative magnetization transfer imaging with few constraints on model parameters.

Improved reconstruction of crossing fibers in the mouse optic pathways with orientation distribution function fingerprinting.

PURPOSE: The accuracy of diffusion MRI tractography reconstruction decreases in the white matter regions with crossing fibers. The optic pathways in rodents provide a challenging structure to test new diffusion tractography approaches because of the small crossing volume within the optic chiasm and the unbalanced 9:1 proportion between the contra- and ipsilateral neural projections from the retina to the lateral geniculate nucleus, respectively. METHODS: Common approaches based on Orientation Distribution Function (ODF) peak finding or statistical inference were compared qualitatively and quantitatively to ODF Fingerprinting (ODF-FP) for reconstruction of crossing fibers within the optic chiasm using in vivo diffusion MRI ( n = 18 $$ n=18 $$ healthy C57BL/6 mice). Manganese-Enhanced MRI (MEMRI) was obtained after intravitreal injection of manganese chloride and used as a reference standard for the optic pathway anatomy. RESULTS: ODF-FP outperformed by over 100% all the tested methods in terms of the ratios between the contra- and ipsilateral segments of the reconstructed optic pathways as well as the spatial overlap between tractography and MEMRI. CONCLUSION: In this challenging model system, ODF-Fingerprinting reduced uncertainty of diffusion tractography for complex structural formations of fiber bundles.

Tractography passes the test: Results from the diffusion-simulated connectivity (disco) challenge.

Estimating structural connectivity from diffusion-weighted magnetic resonance imaging is a challenging task, partly due to the presence of false-positive connections and the misestimation of connection weights. Building on previous efforts, the MICCAI-CDMRI Diffusion-Simulated Connectivity (DiSCo) challenge was carried out to evaluate state-of-the-art connectivity methods using novel large-scale numerical phantoms. The diffusion signal for the phantoms was obtained from Monte Carlo simulations. The results of the challenge suggest that methods selected by the 14 teams participating in the challenge can provide high correlations between estimated and ground-truth connectivity weights, in complex numerical environments. Additionally, the methods used by the participating teams were able to accurately identify the binary connectivity of the numerical dataset. However, specific false positive and false negative connections were consistently estimated across all methods. Although the challenge dataset doesn't capture the complexity of a real brain, it provided unique data with known macrostructure and microstructure ground-truth properties to facilitate the development of connectivity estimation methods.

Surgical cytoreduction of deep-seated high-grade glioma through tubular retractor.

OBJECTIVE: Maximal safe resection is the goal of surgical treatment for high-grade glioma (HGG). Deep-seated hemispheric gliomas present a surgical challenge due to safety concerns and previously were often considered inoperable. The authors hypothesized that use of tubular retractors would allow resection of deep-seated gliomas with an acceptable safety profile. The purpose of this study was to describe surgical outcomes and survival data after resection of deep-seated HGG with stereotactically placed tubular retractors, as well as to discuss the technical advances that enable such procedures. METHODS: This is a retrospective review of 20 consecutive patients who underwent 22 resections of deep-seated hemispheric HGG with the Viewsite Brain Access System by a single surgeon. Patient demographics, survival, tumor characteristics, extent of resection (EOR), and neurological outcomes were recorded. Cannulation trajectories and planned resection volumes depended on the relative location of white matter tracts extracted from diffusion tractography. The surgical plans were designed on the Brainlab system and preoperatively visualized on the Surgical Theater virtual reality SNAP platform. Volumetric assessment of EOR was obtained on the Brainlab platform and confirmed by a board-certified neuroradiologist. RESULTS: Twenty adult patients (18 with IDH-wild-type glioblastomas and 2 with IDH-mutant grade IV astrocytomas) and 22 surgeries were included in the study. The cohort included both newly diagnosed (n = 17; 77%) and recurrent (n = 5; 23%) tumors. Most tumors (64%) abutted the ventricular system. The average preoperative and postoperative tumor volumes measured 33.1 ± 5.3 cm3 and 15.2 ± 5.1 cm3, respectively. The median EOR was 93%. Surgical complications included 2 patients (10%) who developed entrapment of the temporal horn, necessitating placement of a ventriculoperitoneal shunt; 1 patient (5%) who suffered a wound infection and pulmonary embolus; and 1 patient (5%) who developed pneumonia. In 2 cases (9%) patients developed new permanent visual field deficits, and in 5 cases (23%) patients experienced worsening of preoperative deficits. Preoperative neurological or cognitive deficits remained the same in 9 cases (41%) and improved in 7 (32%). The median overall survival was 14.4 months in all patients (n = 20) and in the newly diagnosed IDH-wild-type glioblastoma group (n = 16). CONCLUSIONS: Deep-seated HGGs, which are surgically challenging and frequently considered inoperable, are amenable to resection through tubular retractors, with an acceptable safety profile. Such cytoreductive surgery may allow these patients to experience an overall survival comparable to those with more superficial tumors.

MRI-Visible Anatomy of the Basal Ganglia and Thalamus.

Conventional MR imaging does not discriminate basal ganglia and thalamic internal anatomy well. Radiology reports describe anatomic locations but not specific functional structures. Functional neurosurgery uses indirect targeting based on commissural coordinates or atlases that do not fully account for individual variability. We describe innovative MR imaging sequences that improve the visualization of normal anatomy in this complex brain region and may increase our understanding of basal ganglia and thalamic function. Better visualization also may improve treatments for movement disorders and other emerging functional neurosurgery targets. We aim to provide an accessible review of the most clinically-relevant neuroanatomy within the thalamus and basal ganglia.

MRI-Visible Anatomy of the Brainstem.

Human brainstem internal anatomy is intricate, complex, and essential to normal brain function. The brainstem is affected by stroke, multiple sclerosis, and most neurodegenerative diseases-a 1-mm focus of pathologic condition can have profound clinical consequences. Unfortunately, detailed internal brainstem anatomy is difficult to see with conventional MRI sequences. We review normal brainstem anatomy visualized on widely available clinical 3-T MRI scanners using fast gray matter acquisition T1 inversion recovery, probabilistic diffusion tractography, neuromelanin, and susceptibility-weighted imaging. Better anatomic localization using these recent innovations improves our ability to diagnose, localize, and treat brainstem diseases. We aim to provide an accessible review of the most clinically relevant brainstem neuroanatomy.

mTOR Inhibition with Sirolimus in Multiple System Atrophy: A Randomized, Double-Blind, Placebo-Controlled Futility Trial and 1-Year Biomarker Longitudinal Analysis.

BACKGROUND: Multiple system atrophy (MSA) is a fatal neurodegenerative disease characterized by the aggregation of α-synuclein in glia and neurons. Sirolimus (rapamycin) is an mTOR inhibitor that promotes α-synuclein autophagy and reduces its associated neurotoxicity in preclinical models. OBJECTIVE: To investigate the efficacy and safety of sirolimus in patients with MSA using a futility design. We also analyzed 1-year biomarker trajectories in the trial participants. METHODS: Randomized, double-blind, parallel group, placebo-controlled clinical trial at the New York University of patients with probable MSA randomly assigned (3:1) to sirolimus (2-6 mg daily) for 48 weeks or placebo. Primary endpoint was change in the Unified MSA Rating Scale (UMSARS) total score from baseline to 48 weeks. (ClinicalTrials.gov NCT03589976). RESULTS: The trial was stopped after a pre-planned interim analysis met futility criteria. Between August 15, 2018 and November 15, 2020, 54 participants were screened, and 47 enrolled and randomly assigned (35 sirolimus, 12 placebo). Of those randomized, 34 were included in the intention-to-treat analysis. There was no difference in change from baseline to week 48 between the sirolimus and placebo in UMSARS total score (mean difference, 2.66; 95% CI, -7.35-6.91; P = 0.648). There was no difference in UMSARS-1 and UMSARS-2 scores either. UMSARS scores changes were similar to those reported in natural history studies. Neuroimaging and blood biomarker results were similar in the sirolimus and placebo groups. Adverse events were more frequent with sirolimus. Analysis of 1-year biomarker trajectories in all participants showed that increases in blood neurofilament light chain (NfL) and reductions in whole brain volume correlated best with UMSARS progression. CONCLUSIONS: Sirolimus for 48 weeks was futile to slow the progression of MSA and had no effect on biomarkers compared to placebo. One-year change in blood NfL and whole brain atrophy are promising biomarkers of disease progression for future clinical trials. © 2022 International Parkinson and Movement Disorder Society.

Central Retinal Artery Visualization with Cone-Beam CT Angiography.

Background There are multiple tools available to visualize the retinal and choroidal vasculature of the posterior globe. However, there are currently no reliable in vivo imaging techniques that can visualize the entire retrobulbar course of the retinal and ciliary vessels. Purpose To identify and characterize the central retinal artery (CRA) using cone-beam CT (CBCT) images obtained as part of diagnostic cerebral angiography. Materials and Methods In this retrospective study, patients with catheter DSA performed between October 2019 and October 2020 were included if CBCT angiography included the orbit in the field of view. The CBCT angiography data sets were postprocessed with a small field-of-view volume centered in the posterior globe to a maximum resolution of 0.2 mm. The following were evaluated: CRA origin, CRA course, CRA point of penetration into the optic nerve sheath, bifurcation of the CRA at the papilla, visualization of anatomic variants, and visualization of the central retinal vein. Descriptive statistical analysis was performed. Results Twenty-one patients with 24 visualized orbits were included in the analysis (mean age, 55 years ± 15; 14 women). Indications for angiography were as follows: diagnostic angiography (n = 8), aneurysm treatment (n = 6), or other (n = 7). The CRA was identified in all orbits; the origin, course, point of penetration of the CRA into the optic nerve sheath, and termination in the papilla were visualized in all orbits. The average length of the intraneural segment was 10.6 mm (range, 7-18 mm). The central retinal vein was identified in six of 24 orbits. Conclusion Cone-beam CT, performed during diagnostic angiography, consistently demonstrated the in vivo central retinal artery, demonstrating excellent potential for multiple diagnostic and therapeutic applications. © RSNA, 2021 Online supplemental material is available for this article.

High resolution automated labeling of the hippocampus and amygdala using a 3D convolutional neural network trained on whole brain 700 µm isotropic 7T MP2RAGE MRI.

Image labeling using convolutional neural networks (CNNs) are a template-free alternative to traditional morphometric techniques. We trained a 3D deep CNN to label the hippocampus and amygdala on whole brain 700 µm isotropic 3D MP2RAGE MRI acquired at 7T. Manual labels of the hippocampus and amygdala were used to (i) train the predictive model and (ii) evaluate performance of the model when applied to new scans. Healthy controls and individuals with epilepsy were included in our analyses. Twenty-one healthy controls and sixteen individuals with epilepsy were included in the study. We utilized the recently developed DeepMedic software to train a CNN to label the hippocampus and amygdala based on manual labels. Performance was evaluated by measuring the dice similarity coefficient (DSC) between CNN-based and manual labels. A leave-one-out cross validation scheme was used. CNN-based and manual volume estimates were compared for the left and right hippocampus and amygdala in healthy controls and epilepsy cases. The CNN-based technique successfully labeled the hippocampus and amygdala in all cases. Mean DSC = 0.88 ± 0.03 for the hippocampus and 0.8 ± 0.06 for the amygdala. CNN-based labeling was independent of epilepsy diagnosis in our sample (p = .91). CNN-based volume estimates were highly correlated with manual volume estimates in epilepsy cases and controls. CNNs can label the hippocampus and amygdala on native sub-mm resolution MP2RAGE 7T MRI. Our findings suggest deep learning techniques can advance development of morphometric analysis techniques for high field strength, high spatial resolution brain MRI.

Another 'BEE'? - Brain-Eye-Ear (BEE) Disease Secondary to HbSC Disease Masquerading as Multiple Sclerosis.

Recurrent episodes of neurological dysfunction and white matter lesions in a young adult raise suspicion for multiple sclerosis (MS). However, occlusive retinopathy, hearing loss and absence of CSF oligoclonal bands are atypical for MS and should make the clinician consider an alternative diagnosis. We describe a man with hearing loss, visual signs and symptoms, and an accumulating burden of brain lesions, who was treated for a clinical diagnosis of MS for nearly two decades. Genetic testing revealed a unifying diagnosis.

On the Origins of Diffusion MRI Signal Changes in Stroke.

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.

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

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.

Inner SPACE: 400-Micron Isotropic Resolution MRI of the Human Brain.

OBJECTIVES: Clinically relevant neuroanatomy is challenging to teach, learn and remember since many functionally important structures are visualized best using histology stains from serial 2D planar sections of the brain. In clinical patients, the locations of specific structures then must be inferred from spatial position and surface anatomy. A 3D MRI dataset of neuroanatomy has several advantages including simultaneous multi-planar visualization in the same brain, direct end-user manipulation of the data and image contrast identical to clinical MRI. We created 3D MRI datasets of the postmortem brain with high spatial and contrast resolution for simultaneous multi-planar visualization of complex neuroanatomy. MATERIALS AND METHODS: Whole human brains (N = 6) were immersion-fixed in 4% formaldehyde for 4 weeks, then washed continuously in water for 48 h. The brains were imaged on a clinical 3-T MRI scanner with a 64-channel head and neck coil using a 3D T2-weighted sequence with 400-micron isotropic resolution (voxel = 0.064 mm3; time = 7 h). Besides resolution, this sequence has multiple adjustments to improve contrast compared to a clinical protocol, including 93% reduced turbo factor and 77% reduced effective echo time. RESULTS: This MRI microscopy protocol provided excellent contrast resolution of small nuclei and internal myelinated pathways within the basal ganglia, thalamus, brainstem, and cerebellum. Contrast was sufficient to visualize the presence and variation of horizontal layers in the cerebral cortex. 3D isotropic resolution datasets facilitated simultaneous multi-planar visualization and efficient production of specific tailored oblique image orientations to improve understanding of complex neuroanatomy. CONCLUSION: We created an unlabeled high-resolution digital 3D MRI dataset of neuroanatomy as an online resource for readers to download, manipulate, annotate and use for clinical practice, research, and teaching that is complementary to traditional histology-based atlases. Digital MRI contrast is quantifiable, reproducible across brains and could help validate novel MRI strategies for in vivo structure visualization.

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

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.

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

Beta amyloid (Aß) 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 Aß burden: Aß- [mean mSUVr ≤1.00], Aßi [1.00 < mSUVr <1.17], Aß+ [mSUVr ≥1.17]. Intergroup comparisons of diffusion MRI metrics revealed significant differences across multiple WM tracts. Aßi group displayed more restricted diffusion (higher fractional anisotropy, radial kurtosis, axonal water fraction, and lower radial diffusivity) than both Aß- and Aß+ groups. This nonmonotonic trend was confirmed by significant continuous correlations between mSUVr and diffusion metrics going in opposite direction for 2 cohorts: pooled Aß-/Aßi and pooled Aßi/Aß+. The transient period of increased diffusion restriction may be due to inflammation that accompanies rising Aß burden. In the later stages of Aß accumulation, neurodegeneration is the predominant factor affecting diffusion.

Neuropathologic Changes in Sudden Unexplained Death in Childhood.

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.

Effect of intravoxel incoherent motion on diffusion parameters in normal brain.

At very low diffusion weighting the diffusion MRI signal is affected by intravoxel incoherent motion (IVIM) caused by dephasing of magnetization due to incoherent blood flow in capillaries or other sources of microcirculation. While IVIM measurements at low diffusion weightings have been frequently used to investigate perfusion in the body as well as in malignant tissue, the effect and origin of IVIM in normal brain tissue is not completely established. We investigated the IVIM effect on the brain diffusion MRI signal in a cohort of 137 radiologically-normal patients (62 male; mean age = 50.2 ±â€¯17.8, range = 18 to 94). We compared the diffusion tensor parameters estimated from a mono-exponential fit at b = 0 and 1000 s/mm2 versus at b = 250 and 1000 s/mm2. The asymptotic fitting method allowed for quantitative assessment of the IVIM signal fraction f* in specific brain tissue and regions. Our results show a mean (median) percent difference in the mean diffusivity of about 4.5 (4.9)% in white matter (WM), about 7.8 (8.7)% in cortical gray matter (GM), and 4.3 (4.2)% in thalamus. Corresponding perfusion fraction f* was estimated to be 0.033 (0.032) in WM, 0.066 (0.065) in cortical GM, and 0.033 (0.030) in the thalamus. The effect of f* with respect to age was found to be significant in cortical GM (Pearson correlation ρ â€‹= â€‹0.35, p â€‹= â€‹3*10-5) and the thalamus (Pearson correlation ρ = 0.20, p = 0.022) with an average increase in f* of 5.17*10-4/year and 3.61*10-4/year, respectively. Significant correlations between f* and age were not observed for WM, and corollary analysis revealed no effect of gender on f*. Possible origins of the IVIM effect in normal brain tissue are discussed.