Restriction Spectrum Imaging Research Articles

General Psychopathology, Cognition, and the Cerebral Cortex in 10-Year-Old Children: Insights From the Adolescent Brain Cognitive Development Study.

General psychopathology and cognition are likely to have a bidirectional influence on each other. Yet, the relationship between brain structure, psychopathology, and cognition remains unclear. This brief report investigates the association between structural properties of the cerebral cortex [surface area, cortical thickness, intracortical myelination indexed by the T1w/T2w ratio, and neurite density assessed by restriction spectrum imaging (RSI)] with general psychopathology and cognition in a sample of children from the Adolescent Brain Cognitive Development (ABCD) study. Higher levels of psychopathology and lower levels of cognitive ability were associated with a smaller cortical surface area. Inter-regionally—across the cerebral cortex—the strength of association between an area and psychopathology is strongly correlated with the strength of association between an area and cognition. Taken together, structural deviations particularly observed in the cortical surface area influence both psychopathology and cognition.

Associations between MRI-assessed locus coeruleus integrity and cortical gray matter microstructure.

The locus coeruleus (LC) is one of the earliest sites of tau pathology, making it a key structure in early Alzheimer's disease (AD) progression. As the primary source of norepinephrine for the brain, reduced LC integrity may have negative consequences for brain health, yet macrostructural brain measures (e.g. cortical thickness) may not be sensitive to early stages of neurodegeneration. We therefore examined whether LC integrity was associated with differences in cortical gray matter microstructure among 435 men (mean age = 67.5; range = 62-71.7). LC structural integrity was indexed by contrast-to-noise ratio (LCCNR) from a neuromelanin-sensitive MRI scan. Restriction spectrum imaging (RSI), an advanced multi-shell diffusion technique, was used to characterize cortical microstructure, modeling total diffusion in restricted, hindered, and free water compartments. Higher LCCNR (greater integrity) was associated with higher hindered and lower free water diffusion in multiple cortical regions. In contrast, no associations between LCCNR and cortical thickness survived correction. Results suggest lower LC integrity is associated with patterns of cortical microstructure that may reflect a reduction in cytoarchitectural barriers due to broader neurodegenerative processes. These findings highlight the potential utility for LC imaging and advanced diffusion measures of cortical microstructure in assessing brain health and early identification of neurodegenerative processes.

Characterization of the diffusion signal of breast tissues using multi-exponential models.

Restriction spectrum imaging (RSI) decomposes the diffusion-weighted MRI signal into separate components of known apparent diffusion coefficients (ADCs). The number of diffusion components and optimal ADCs for RSI are organ-specific and determined empirically. The purpose of this work was to determine the RSI model for breast tissues. The diffusion-weighted MRI signal was described using a linear combination of multiple exponential components. A set of ADC values was estimated to fit voxels in cancer and control ROIs. Later, the signal contributions of each diffusion component were estimated using these fixed ADC values. Relative-fitting residuals and Bayesian information criterion were assessed. Contrast-to-noise ratio between cancer and fibroglandular tissue in RSI-derived signal contribution maps was compared to DCE imaging. A total of 74 women with breast cancer were scanned at 3.0 Tesla MRI. The fitting residuals of conventional ADC and Bayesian information criterion suggest that a 3-component model improves the characterization of the diffusion signal over a biexponential model. Estimated ADCs of triexponential model were D1,3 = 0, D2,3 = 1.5 × 10-3 , and D3,3 = 10.8 × 10-3 mm2 /s. The RSI-derived signal contributions of the slower diffusion components were larger in tumors than in fibroglandular tissues. Further, the contrast-to-noise and specificity at 80% sensitivity of DCE and a subset of RSI-derived maps were equivalent. Breast diffusion-weighted MRI signal was best described using a triexponential model. Tumor conspicuity in breast RSI model is comparable to that of DCE without the use of exogenous contrast. These data may be used as differential features between healthy and malignant breast tissues.

Association of Outdoor Ambient Fine Particulate Matter With Intracellular White Matter Microstructural Properties Among Children

Outdoor particulate matter 2.5 μm or less in diameter (PM2.5) is a ubiquitous environmental neurotoxicant that may affect the developing brain. Little is known about associations between PM2.5 and white matter connectivity. To assess associations between annual residential PM2.5 exposure and white matter microstructure health in a US sample of children 9 to 10 years of age and to examine whether associations are specific to certain white matter pathways or vary across neuroimaging diffusion markers reflective of intracellular and extracellular microstructural processes. This cross-sectional study, the Adolescent Brain and Cognitive Development (ABCD) Study, was composed of 21 study sites across the US and used baseline data collected from children 9 to 10 years of age from September 1, 2016, to October 15, 2018. Data analysis was performed from September 15, 2020, to June 30, 2021. Annual mean PM2.5 exposure estimated by ensemble-based models and assigned to the primary residential addresses at baseline. Diffusion-weighted imaging (DWI) and tractography were used to delineate white matter tracts. The biophysical modeling technique of restriction spectrum imaging (RSI) was implemented to examine total hindered diffusion and restricted isotropic and anisotropic intracellular diffusion in each tract. Hierarchical mixed-effects models with natural splines were used to analyze the associations between PM2.5 exposure and DWI. In a study population of 7602 children (mean [SD] age, 119.1 [7.42] months; 3955 [52.0%] female; 160 [ 21.%] Asian, 1025 [13.5%] Black, 1616 [21.3%] Hispanic, 4025 [52.9%] White, and 774 [10.2%] other [identified by parents as American Indian/Native American or Alaska Native; Native Hawaiian, Guamanian, Samoan, other Pacific Islander; Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, or other Asian; or other race]), associations were seen between annual ambient PM2.5 and hemispheric differences in white matter microstructure. Hemisphere-stratified models revealed significant associations between PM2.5 exposure and restricted isotropic intracellular diffusion in the left cingulum, in the left superior longitudinal fasciculus, and bilaterally in the fornix and uncinate fasciculus. In tracts with strong positive associations, a PM2.5 increase from 8 to 12 μg/m3 was associated with increases of 2.16% (95% CI, 0.49%-3.84%) in the left cingulum, 1.95% (95% CI, 0.43%-3.47%) in the left uncinate, and 1.68% (95% CI, 0.01%-3.34%) in the right uncinate. Widespread negative associations were observed between PM2.5 and mean diffusivity. The findings of this cross-sectional study suggest that annual mean PM2.5 exposure during childhood is associated with increased restricted isotropic diffusion and decreased mean diffusivity of specific white matter tracts, potentially reflecting differences in the composition of white matter microarchitecture.

Microstructural development from 9 to 14 years: Evidence from the ABCD Study

During late childhood behavioral changes, such as increased risk-taking and emotional reactivity, have been associated with the maturation of cortico-cortico and cortico-subcortical circuits. Understanding microstructural changes in both white matter and subcortical regions may aid our understanding of how individual differences in these behaviors emerge. Restriction spectrum imaging (RSI) is a framework for modelling diffusion-weighted imaging that decomposes the diffusion signal from a voxel into hindered, restricted, and free compartments. This yields greater specificity than conventional methods of characterizing diffusion. Using RSI, we quantified voxelwise restricted diffusion across the brain and measured age associations in a large sample (n = 8086) from the Adolescent Brain and Cognitive Development (ABCD) study aged 9–14 years. Older participants showed a higher restricted signal fraction across the brain, with the largest associations in subcortical regions, particularly the basal ganglia and ventral diencephalon. Importantly, age associations varied with respect to the cytoarchitecture within white matter fiber tracts and subcortical structures, for example age associations differed across thalamic nuclei. This suggests that age-related changes may map onto specific cell populations or circuits and highlights the utility of voxelwise compared to ROI-wise analyses. Future analyses will aim to understand the relevance of this microstructural developmental for behavioral outcomes.

Brain microstructure mediates effects of tau on cognitive decline in early Alzheimer’s disease

AbstractBackgroundTau propagation from medial temporal regions to neocortex correlates with cognitive decline and neurodegeneration. Microstructural damage to medial temporal gray matter and associated white matter predicts Alzheimer’s disease (AD)‐related cognitive impairment. However, whether brain cytoarchitectural injury mediates effects of tau on cognitive dysfunction, or promotes cognitive decline via convergent pathways, remains unresolved.MethodWe used restriction spectrum imaging (RSI) to identify microstructural brain abnormalities associated with total tau, and to determine whether they mediate tau‐related cognitive decline. RSI, cerebrospinal fluid total tau, global cognitive function and verbal episodic memory data were acquired on 34 participants ranging from cognitively normal to mild AD (21 normal controls, 13 cognitively impaired (mild cognitive impairment or early AD)). Longitudinal RSI and cognitive data were collected two and four years post‐baseline, respectively. Restricted isotropic diffusion (RI), neurite density (ND), and isotropic free water (IF) were computed in hippocampus, entorhinal cortex, and six white matter tracts. Partial correlations examined associations among tau, microstructure, and cognition and mediation analyses assessed whether microstructure mediates tau‐related cognitive decline. Linear regressions compared the sensitivity of tau, amyloid and microstructure to cognitive outcomes. Partial correlations tested whether tau predicts subsequent microstructural change.ResultTau most strongly correlated with reduced RI, a measure of intracellular integrity, in the hippocampus and fornix. Tau and microstructure in all examined regions correlated with baseline and longitudinal cognitive performance. Hippocampal and fornix RI mediated effects of tau on cross‐sectional memory and global cognitive function, but direct effects of tau on cognition were not significant. White matter and entorhinal microstructure better predicted baseline memory and global cognition, and hippocampal IF better predicted global cognitive decline, than did tau or amyloid. Tau predicted more rapid decline in white matter RI and ND.ConclusionMarkers of tau‐related neurodegeneration may reflect hippocampal and fornix injury that promotes memory impairment and dementia progression. However, medial temporal and white matter microstructure better predicts cognitive outcomes than tau and amyloid, implicating additional factors contributing to neural injury underlying cognitive decline. RSI may be useful for identifying microstructural brain abnormalities consequent to AD pathology or other risk factors, that signal early cognitive dysfunction.

Associations between MRI‐assessed locus coeruleus integrity and restriction spectrum imaging of cortical gray matter microstructure

AbstractBackgroundThe locus coeruleus (LC) serves as the primary source of norepinephrine for the brain. Findings that the LC is one of the earliest sites of tau pathology make it a key structure in the early stages of Alzheimer’s disease (AD) progression. An important question is whether measures of LC integrity are associated with indexes of brain structure that may suggest broader patterns of neurodegeneration, particularly if such patterns are detectable prior to substantial macrostructural change. We therefore examined whether LC structural integrity was associated with differences in cortical gray matter microstructure among adults in early old age.MethodParticipants were 435 men (mean age=67.5; range=62‐71.7) from the Vietnam Era Twin Study of Aging (VETSA). Rostral LC structural integrity was indexed by contrast‐to‐noise ratio (LCCNR) from a neuromelanin‐sensitive MRI scan. Restriction spectrum imaging (RSI), an advanced multi‐shell diffusion technique, was used to characterize cortical microstructure, modeling diffusion in restricted, hindered, and free water compartments. Associations between LCCNR and isotropic diffusion within each compartment were examined for bilateral averages of 34 cortical ROIs defined by the Desikan‐Killiany parcellation. As a sensitivity analysis, we also examined whether LCCNR was associated with mean diffusivity (MD), a conventional diffusion tensor imaging (DTI) metric, or cortical thickness in the same regions.ResultAfter correction for multiple comparisons, higher LCCNR (greater structural integrity) was significantly associated with higher hindered isotropic diffusion and lower free water diffusion across multiple brain regions. In contrast, LCCNR was only associated with lower MD in one brain region and there were no associations with cortical thickness after correction.ConclusionThese results provide evidence that lower MRI‐assessed LC integrity is associated with patterns of cortical microstructure that may reflect a reduction in cellular membranes due to broader neurodegenerative processes. Individual differences in LC integrity were only detected with more advanced measures of microstructure that may be more sensitive to early changes than conventional diffusion imaging or macrostructural measures. These results highlight the potential utility for MRI of the LC and cortical microstructure in early identification of AD risk.

Voxel-level Classification of Prostate Cancer on Magnetic Resonance Imaging: Improving Accuracy Using Four-Compartment Restriction Spectrum Imaging.

Diffusion magnetic resonance imaging (MRI) is integral to detection of prostate cancer (PCa), but conventional apparent diffusion coefficient (ADC) cannot capture the complexity of prostate tissues and tends to yield noisy images that do not distinctly highlight cancer. A four-compartment restriction spectrum imaging (RSI4 ) model was recently found to optimally characterize pelvic diffusion signals, and the model coefficient for the slowest diffusion compartment, RSI4 -C1 , yielded greatest tumor conspicuity. To evaluate the slowest diffusion compartment of a four-compartment spectrum imaging model (RSI4 -C1 ) as a quantitative voxel-level classifier of PCa. Retrospective. Forty-six men who underwent an extended MRI acquisition protocol for suspected PCa. Twenty-three men had benign prostates, and the other 23 men had PCa. A 3 T, multishell diffusion-weighted and axial T2-weighted sequences. High-confidence cancer voxels were delineated by expert consensus, using imaging data and biopsy results. The entire prostate was considered benign in patients with no detectable cancer. Diffusion images were used to calculate RSI4 -C1 and conventional ADC. Classifier images were also generated. Voxel-level discrimination of PCa from benign prostate tissue was assessed via receiver operating characteristic (ROC) curves generated by bootstrapping with patient-level case resampling. RSI4 -C1 was compared to conventional ADC for two metrics: area under the ROC curve (AUC) and false-positive rate for a sensitivity of 90% (FPR90 ). Statistical significance was assessed using bootstrap difference with two-sided α=0.05. RSI4 -C1 outperformed conventional ADC, with greater AUC (mean 0.977 [95% CI: 0.951-0.991] vs. 0.922 [0.878-0.948]) and lower FPR90 (0.032 [0.009-0.082] vs. 0.201 [0.132-0.290]). These improvements were statistically significant (P < 0.05). RSI4 -C1 yielded a quantitative, voxel-level classifier of PCa that was superior to conventional ADC. RSI classifier images with a low false-positive rate might improve PCa detection and facilitate clinical applications like targeted biopsy and treatment planning. 3 TECHNICAL EFFICACY: Stage 2.

Brain microstructure mediates sex-specific patterns of cognitive aging.

Normal brain aging is characterized by declining neuronal integrity, yet it remains unclear how microstructural injury influences cognitive aging and whether such mechanisms differ between sexes. Using restriction spectrum imaging (RSI), we examined sex differences in associations between brain microstructure and cognitive function in 147 community-dwelling older men and women (56-99 years). Gray and white matter microstructure correlated with global cognition, executive function, visuospatial memory, episodic memory, and logical memory, with the strongest associations for restricted, hindered and free isotropic diffusion. Associations were stronger for women than for men, a difference likely due to greater age-related variability in cognitive scores and microstructure in women. Isotropic diffusion mediated effects of age on cognition for both sexes, though distinct mediation patterns were present for women and men. For women, hippocampal and corpus callosum microstructure mediated age effects on verbal and visuospatial memory, respectively, whereas for men fiber microstructure (mainly fornix and corpus callosum) mediated age effects on executive function and visuospatial memory. These findings implicate sex-specific pathways by which changing brain cytoarchitecture contributes to cognitive aging, and suggest that RSI may be useful for evaluating risk for cognitive decline or monitoring efficacy of interventions to preserve brain health in later life.

Age and Sex Differences in the Associations of Pulse Pressure With White Matter and Subcortical Microstructure.

Midlife vascular disease increases risk for dementia and effects of vascular dysfunction on brain health differ between men and women. Elevated pulse pressure, a surrogate for arterial stiffness, contributes to cerebrovascular pathology and white matter damage that may advance cognitive aging; however, it remains unclear how associations between pulse pressure and neural integrity differ by sex and age. This study used restriction spectrum imaging to examine associations between pulse pressure and brain microstructure in community-dwelling women (N=88) and men (N=55), aged 56 to 97 (mean, 76.3) years. Restricted isotropic (presumed intracellular), hindered isotropic (presumed extracellular), neurite density, and free water diffusion were computed in white matter tracts and subcortical regions. After adjustment for age and sex, higher pulse pressure correlated with lower restricted isotropic diffusion in global white matter, with more pronounced associations in parahippocampal cingulum, as well as in thalamus and hippocampus. Subgroup analyses demonstrated stronger correlations between pulse pressure and restricted isotropic diffusion in association fibers for participants ≤75 years than for older participants, with stronger effects for women than men of this age group. Microstructure in parahippocampal cingulum and thalamus differed by pulse pressure level regardless of antihypertensive treatment. Increased pulse pressure may lead to widespread injury to white matter and subcortical structures, with greatest vulnerability for women in late middle to early older age. Restriction spectrum imaging could be useful for monitoring microstructural changes indicative of neuronal loss or shrinkage, demyelination, or inflammation that accompany age-related cerebrovascular dysfunction.

Altered hippocampal microstructure and function in children who experienced Hurricane Irma.

Hurricane Irma was the most powerful Atlantic hurricane in recorded history, displacing 6 million and killing over 120 people in the state of Florida alone. Unpredictable disasters like Irma are associated with poor cognitive and health outcomes that can disproportionately impact children. This study examined the effects of Hurricane Irma on the hippocampus and memory processes previously related to unpredictable stress. We used an innovative application of an advanced diffusion‐weighted imaging technique, restriction spectrum imaging (RSI), to characterize hippocampal microstructure (i.e., cell density) in 9‐ to 10‐year‐old children who were exposed to Hurricane Irma relative to a non‐exposed control group (i.e., assessed the year before Hurricane Irma). We tested the hypotheses that the experience of Hurricane Irma would be associated with decreases in: (a) hippocampal cellularity (e.g., neurogenesis), based on known associations between unpredictable stress and hippocampal alterations; and (b) hippocampal‐related memory function as indexed by delayed recall. We show an association between decreased hippocampal cellularity and delayed recall memory in children who experienced Hurricane Irma relative to those who did not. These findings suggest an important role of RSI for assessing subtle microstructural changes related to functionally significant changes in the developing brain in response to environmental events.

Multiparametric MRI in the Diagnosis of Prostate Cancer: Physical Foundations, Limitations, and Prospective Advances ofDiffusion-Weighted MRI.

Diffusion-weighted imaging (DWI) is an essential component of the multiparametric MRI exam for the diagnosis and assessment of prostate cancer (PCa). Over the last two decades, various models have been developed to quantitatively correlate the DWI signal with microstructural characteristics of prostate tissue. The simplest approach (ADC: apparent diffusion coefficient) - currently established as the clinical standard - describes monoexponential decay of the DWI signal. While numerous studies have shown an inverse correlation of ADC values with the Gleason score, the ADC model lacks specificity and is based on water diffusion dynamics that are not true in human tissue. This article aims to explain the biophysical limitations of the standard DWI model and to discuss the potential of more complex, advanced DWI models. This article is a review based on a selective literature review. Four phenomenological DWI models are introduced: diffusion tensor imaging, intravoxel incoherent motion, biexponential model, and diffusion kurtosis imaging. Their parameters may potentially improve PCa diagnostics but show varying degrees of statistical significance with respect to the detection and characterization of PCa in current studies. Phenomenological model parameters lack specificity, which has motivated the development of more descriptive tissue models that directly relate microstructural features to the DWI signal. Finally, we present two of such structural models, i. e. the VERDICT (Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumors) and RSI (Restriction Spectrum Imaging) model. Both have shown promising results in initial studies regarding the characterization and prognosis of PCa. Recent developments in DWI techniques promise increasing accuracy and more specific statements about microstructural changes of PCa. However, further studies are necessary to establish a standardized DWI protocol for the diagnosis of PCa. · DWI is paramount to the mpMRI exam for the diagnosis of PCa.. · Though of clinical value, the ADC model lacks specificity and oversimplifies tissue complexities.. · Advanced phenomenological and structural models have been developed to describe the DWI signal.. · Phenomenological models may improve diagnostics but show inconsistent results regarding PCa assessment.. · Structural models have demonstrated promising results in initial studies regarding PCa characterization.. · Wichtmann BD, Zöllner FG, Attenberger UI et al. Multiparametric MRI in the Diagnosis of Prostate Cancer: Physical Foundations, Limitations, and Prospective Advances of Diffusion-Weighted MRI. Fortschr Röntgenstr 2021; 193: 399 - 409.

P.408 Electroconvulsive therapy induces immediate changes in the extraneurite water compartment: a restriction spectrum imaging study

P.408 Electroconvulsive therapy induces immediate changes in the extraneurite water compartment: a restriction spectrum imaging study

Nucleus accumbens cytoarchitecture predicts weight gain in children

The prevalence of obesity in children and adolescents worldwide has quadrupled since 1975 and is a key predictor of obesity later in life. Previous work has consistently observed relationships between macroscale measures of reward-related brain regions (e.g., the nucleus accumbens [NAcc]) and unhealthy eating behaviors and outcomes; however, the mechanisms underlying these associations remain unclear. Recent work has highlighted a potential role of neuroinflammation in the NAcc in animal models of diet-induced obesity. Here, we leverage a diffusion MRI technique, restriction spectrum imaging, to probe the microstructure (cellular density) of subcortical brain regions. More specifically, we test the hypothesis that the cell density of reward-related regions is associated with obesity-related metrics and early weight gain. In a large cohort of nine- and ten-year-olds enrolled in the Adolescent Brain Cognitive Development (ABCD) study, we demonstrate that cellular density in the NAcc is related to individual differences in waist circumference at baseline and is predictive of increases in waist circumference after 1 y. These findings suggest a neurobiological mechanism for pediatric obesity consistent with rodent work showing that high saturated fat diets increase gliosis and neuroinflammation in reward-related brain regions, which in turn lead to further unhealthy eating and obesity.

White matter microstructure across the adult lifespan: A mixed longitudinal and cross-sectional study using advanced diffusion models and brain-age prediction

The macro- and microstructural architecture of human brain white matter undergoes substantial alterations throughout development and ageing. Most of our understanding of the spatial and temporal characteristics of these lifespan adaptations come from magnetic resonance imaging (MRI), including diffusion MRI (dMRI), which enables visualisation and quantification of brain white matter with unprecedented sensitivity and detail. However, with some notable exceptions, previous studies have relied on cross-sectional designs, limited age ranges, and diffusion tensor imaging (DTI) based on conventional single-shell dMRI. In this mixed cross-sectional and longitudinal study (mean interval: 15.2 months) including 702 multi-shell dMRI datasets, we combined complementary dMRI models to investigate age trajectories in healthy individuals aged 18 to 94 years (57.12% women). Using linear mixed effect models and machine learning based brain age prediction, we assessed the age-dependence of diffusion metrics, and compared the age prediction accuracy of six different diffusion models, including diffusion tensor (DTI) and kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI), restriction spectrum imaging (RSI), spherical mean technique multi-compartment (SMT-mc), and white matter tract integrity (WMTI). The results showed that the age slopes for conventional DTI metrics (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity [AD], radial diffusivity [RD]) were largely consistent with previous research, and that the highest performing advanced dMRI models showed comparable age prediction accuracy to conventional DTI. Linear mixed effects models and Wilk's theorem analysis showed that the ‘FA fine’ metric of the RSI model and ‘orientation dispersion’ (OD) metric of the NODDI model showed the highest sensitivity to age. The results indicate that advanced diffusion models (DKI, NODDI, RSI, SMT mc, WMTI) provide sensitive measures of age-related microstructural changes of white matter in the brain that complement and extend the contribution of conventional DTI.

Diagnostic utility of Restriction Spectrum Imaging in the characterization of the peritumoral brain zone in glioblastoma: Analysis of overall and progression-free survival

PurposeWe studied the ability of Restriction Spectrum Imaging (RSI), a novel advanced diffusion imaging technique, to estimate levels of cellularity in different glioblastoma regions, evaluated their prognostic value compared with established clinical diffusion metrics such as fractional anisotropy (FA) and mean diffusivity (MD). MethodsForty-two patients with untreated glioblastoma, IDH-wildtype, were examined with an advanced MRI tumor protocol. The region of interest (ROI) was obtained from the contrast-enhancing part of tumor and the peritumoral brain zones and then co-registered with RSI-cellularity index, FA and MD maps. Histogram parameters of diffusion metrics were assessed for all ROI locations and compared to MGMT promoter methylation status and survival. The ability of RSI-cellularity index, FA, and MD to stratify survival and were assessed by Cox proportional hazard regression, adjusted for significant clinical predictors. ResultsThe highest RSI-cellularity index was measured in contrast-enhancing tumor core with a negative gradient from tumor core to the periphery of peritumoral zone with predictive accuracy 81 % (P < 0.001). Shorter overall survival was significant associated with higher RSI-cellularity index (hazard ratio (HR) 3.6, 95 % confidence interval (CI) 1.3−9.5, P = 0.002) with synchronal decrease in MD (HR 0.31, 95 %CI 0.1−0.8, P = 0.008) in the contrast-enhanced tumor core. This association was also consistent for RSI-cellularity index value measured in the peri-enhancing zone (HR 3.6, 95 % CI 1.0−12.3, P = 0.041). No statistically significant differences were noted between RSI-cellularity index, FA, nor MD and MGMT promoter methylation. ConclusionRSI-cellularity index may be used as prognostic biomarker to improve risk stratification in patients with glioblastoma.

Associations between age and brain microstructure in older community-dwelling men and women: the Rancho Bernardo Study

Cytoarchitectural brain changes during normal aging remain poorly characterized, and it is unclear whether patterns of brain aging differ by sex. This study used restriction spectrum imaging to examine associations between age and brain microstructure in 147 community-dwelling participants (aged 56-99 years). Widespread associations with age in multiple diffusion compartments, including increased free water, decreased restricted and hindered diffusion, and reduced neurite complexity, were observed in the cortical gray matter, the white matter tracts, and the hippocampus. Age differences in cortical microstructure were largely independent of atrophy. Associations were mostly global, although foci of stronger effects emerged in the fornix, anterior thalamic radiation and commissural fibers, and the medial temporal, orbitofrontal, and occipital cortices. Age differences were stronger and more widespread for women than men, even after adjustment for education, hypertension, and body mass index. Restriction spectrum imaging may be a convenient, noninvasive tool for monitoring changes in diffusion properties that are thought to reflect reduced cellular fractions and neurite density or complexity, which occur with typical aging, and for detecting sex differences in patterns of brain aging.

New prostate MRI techniques and sequences.

Prostate MRI has seen increasing interest in recent years and has led to the development of new MRI techniques and sequences to improve prostate cancer (PCa) diagnosis which are reviewed in this article. Numerous studies have focused on improving image quality (segmented DWI) and faster acquisition (compressed sensing, k-t-SENSE, PROPELLER). An increasing number of studies have developed new quantitative and computer-aided diagnosis methods including artificial intelligence (PROSTATEx challenge) that mitigate the subjective nature of mpMRI interpretation. MR fingerprinting allows rapid, simultaneous generation of quantitative maps of multiple physical properties (T1, T2), where PCa are characterized by lower T1 and T2 values. New techniques like luminal water imaging (LWI), restriction spectrum imaging (RSI), VERDICT and hybrid multi-dimensional MRI (HM-MRI) have been developed for microstructure imaging, which provide information similar to histology. The distinct MR properties of tissue components and their change with the presence of cancer is used to diagnose prostate cancer. LWI is a T2-based imaging technique where long T2-component corresponding to luminal water is reduced in PCa. RSI and VERDICT are diffusion-based techniques where PCa is characterized by increased signal from intra-cellular restricted water and increased intracellular volume fraction, respectively, due to increased cellularity. VERDICT also reveal loss of extracellular-extravascular space in PCa due to loss of glandular structure. HM-MRI measures volumes of prostate tissue components, where PCa has reduced lumen and stromal and increased epithelium volume similar to results shown in histology. Similarly, molecular imaging using hyperpolarized 13C imaging has been utilized.

PD54-10 RESTRICTED SPECTRUM IMAGING-MRI: AN EFFECTIVE AND NON-INVASIVE BIOMARKER TO REDUCE FALSE POSITIVE LESIONS AND DETECT UPGRADED PROSTATE CANCER IN MEN ON ACTIVE SURVEILLANCE

INTRODUCTION AND OBJECTIVE:We investigated the utility of an advanced multi-compartment diffusion model using the Restriction Spectrum Imaging (RSI-MRI) to identify areas of restricted water and pr...

Associations Between Microstructure, Amyloid, and Cognition in Amnestic Mild Cognitive Impairment and Dementia.

Although amyloid-β (Aβ) and microstructural brain changes are both effective biomarkers of Alzheimer's disease, their independent or synergistic effects on cognitive decline are unclear. To examine associations of Aβ and brain microstructure with cognitive decline in amnestic mild cognitive impairment and dementia. Restriction spectrum imaging, cerebrospinal fluid Aβ, and longitudinal cognitive data were collected on 23 healthy controls and 13 individuals with mild cognitive impairment or mild to moderate Alzheimer's disease. Neurite density (ND) and isotropic free water diffusion (IF) were computed in fiber tracts and cortical regions of interest. We examined associations of Aβ with regional and whole-brain microstructure, and assessed whether microstructure mediates effects of Aβ on cognitive decline. Lower ND in limbic and association fibers and higher medial temporal lobe IF predicted baseline impairment and longitudinal decline across multiple cognitive domains. ND and IF predicted cognitive outcomes after adjustment for Aβ or whole-brain microstructure. Correlations between microstructure and cognition were present for both amyloid-positive and amyloid-negative individuals. Aβ correlated with whole-brain, rather than regional, ND and IF. Aβ correlates with widespread microstructural brain changes, whereas regional microstructure correlates with cognitive decline. Microstructural abnormalities predict cognitive decline regardless of amyloid, and may inform about neural injury leading to cognitive decline beyond that attributable to amyloid.