Diffusion Weighted Imaging Metrics Research Articles

The impact of diffusion and perfusion-weighted imaging on glioma grading

Abstract Objectives Determining the grade of a glioma is extremely important for treatment planning and prognosis prediction. The study aimed to evaluate the usefulness of multiparametric perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) in preoperative glioma grading. Methods In this retrospective study, 63 individuals with brain tumors histologically confirmed, of which 23 had low-grade gliomas (LGGs) and 40 had high-grade gliomas (HGGs) were involved. We conducted this paper on apparent diffusion coefficient (ADC) maps using the entire tumor volume method, allowing us to use all ADC values of the tumor. Small-sample regions of interest (ROIs) were drawn to collect parameters of relative cerebral blood flow (rCBF), cerebral blood flow (CBF), and relative cerebral blood volume (rCBV), from both the tumor core and peritumoral edema. The PWI and DWI metrics were compared to identify the most accurate distinguishing HGGs and LGGs, analyze receiver operating characteristics (ROC), and evaluate the diagnostic performance using solitary parameters and combined. Results In diffusion MRI, there were significant differences in minimum ADC and mean ADC between LGGs and HGGs (p<0.05), with the larger area under the curve (AUC) of 0.898 found for mean ADC at a cut-off value of 1.275, with sensitivity of 82.6 % and specificity of 90 %. The maximum ADC value did not differ significantly (p>0.05). All perfusion parameters in both the tumor core and peritumoral edema area were significantly greater values in cases of HGG compared to LGG (p<0.001), with the highest AUC of 0.946 found for solid tumor rCBV value (rCBVt), the cut-off is 3.585, sensitivity of 85 % and specificity of 100 %. Combining mean ADC and rCBVt provided an excellent AUC of 0.975, a sensitivity of 92.5 %, and a specificity of 91.3 % for differentiating between HGGs and LGGs. Conclusions Perfusion and diffusion MRI are valuable in discriminating between high-grade and low-grade gliomas, with the major criterion in the decision-making process being the combined mean ADC and rCBVt parameters.

MRI and Blood-based Biomarkers Are Associated With Surgery in Children and Adults With Ileal Crohn's Disease.

Despite advances in medical therapy, many children and adults with ileal Crohn's disease (CD) progress to fibrostenosis requiring surgery. We aimed to identify MRI and circulating biomarkers associated with the need for surgical management. This prospective, multicenter study included pediatric and adult CD cases undergoing ileal resection and CD controls receiving medical therapy. Noncontrast research MRI examinations measured bowel wall 3-dimensional magnetization transfer ratio normalized to skeletal muscle (normalized 3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, intravoxel incoherent motion (IVIM) diffusion-weighted imaging metrics, and the simplified magnetic resonance index of activity (sMaRIA). Circulating biomarkers were measured on the same day as the research MRI and included CD64, extracellular matrix protein 1 (ECM1), and granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (Ab). Associations between MRI and circulating biomarkers and need for ileal resection were tested using univariate and multivariable LASSO regression. Our study sample included 50 patients with CD undergoing ileal resection and 83 patients with CD receiving medical therapy; mean participant age was 23.9 ± 13.1 years. Disease duration and treatment exposures did not vary between the groups. Univariate biomarker associations with ileal resection included log GM-CSF Ab (odds ratio [OR], 2.87; P = .0009), normalized 3D MTR (OR, 1.05; P = .002), log MOLLI T1 (OR, 0.01; P = .02), log IVIM perfusion fraction (f; OR, 0.38; P = .04), and IVIM apparent diffusion coefficient (ADC; OR, 0.3; P = .001). The multivariable model for surgery based upon correctedAkaike information criterion included age (OR, 1.03; P = .29), BMI (OR, 0.91; P = .09), log GM-CSF Ab (OR, 3.37; P = .01), normalized 3D MTR (OR, 1.07; P = .007), sMaRIA (OR, 1.14; P = .61), luminal narrowing (OR, 10.19; P = .003), log C-reactive protein (normalized; OR, 2.75; P = .10), and hematocrit (OR, 0.90; P = .13). After accounting for clinical and MRI measures of severity, normalized 3D MTR and GM-CSF Ab are associated with the need for surgery in ileal CD.

MRI AND BLOOD-BASED BIOMARKERS ASSOCIATED WITH SURGICAL MANAGEMENT IN CHILDREN AND ADULTS WITH SMALL BOWEL CROHN'S DISEASE

Abstract BACKGROUND Despite advances in medical therapy, many children and adults with ileal Crohn’s Disease (CD) progress to fibrostenosis requiring surgery. Prior studies have identified circulating and imaging biomarkers associated with strictures, although their associations with need for surgery are not well-established. PURPOSE We aimed to identify MRI and circulating biomarkers associated with the need for surgical management in chidlren and adults with ileal CD. METHODS This prospective, multi-center study included pediatric and adult CD cases undergoing ileal resection (n=50), and CD controls receiving medical therapy (n=83). Noncontrast research MRI examinations measured bowel wall three-dimensional magnetization transfer ratio normalized to skeletal muscle (normalized 3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, intravoxel incoherent motion (IVIM) diffusion-weighted imaging metrics, and the simplified magnetic resonance index of activity (sMaRIA) (Figure 1). Circulating biomarkers included CD64, ECM1, and GM-CSF autoantibodies (Ab). Clinical variables, including demographics, anthropometrics, and routine clinical laboratory data (e.g., CRP, fecal calprotectin), also were obtained at the research visit. Associations between MRI and circulating biomarkers and need for ileal resection were tested using univariate and multivariable LASSO regression. RESULTS Mean participant age was 23.9±13.1 years. Disease duration and treatment exposures did not vary between the groups. Univariate biomarker associations with ileal resection included log GM-CSF Ab (odds ratio [OR]=2.87; p=0.0009), normalized 3D MTR (OR=1.05; p=0.002), log MOLLI T1 (OR=0.01; p=0.02), log IVIM perfusion fraction (f) (OR=0.38; p=0.04), and IVIM apparent diffusion coefficient (ADC) (OR=0.3; p=0.001). MRI and circulating biomarker Tukey box plots are presented in Figure 2. The multivariable model for surgery based upon AICc criteria included age (OR=1.03; p=0.29), BMI (OR=0.91; p=0.09), log GM-CSF Ab (OR=3.37; p=0.01), normalized 3D MTR (OR=1.07; p=0.007), sMaRIA (OR=1.14; p=0.61), luminal narrowing (OR=10.19; p=0.003), log CRP (normalized) (OR=2.75; p=0.10), and hematocrit (OR=0.90; p=0.13). CONCLUSION After accounting for clinical and MRI measures of severity, normalized 3D MTR and GM-CSF Ab are associated with need for surgery in ileal CD. GM-CSF autoantibodies and MRI biomarker sequences may be useful for guiding management decisions in CD patients. Figure 1 Research MRI images from a surgical Crohn’s disease patient with stricturing behavior involving the terminal ileum. A and B. Coronal and axial fat-saturated T2-weighted single-shot fast spin-echo (SSFSE) images show wall thickening and luminal narrowing of the terminal ileum (arrows) with more proximal bowel dilation measuring greater than 3 cm. C. Axial 3D magnetization transfer images – MT pulse on (bottom image, arrow), MT pulse off (top image, arrow). D. Axial modified Look-Locker inversion recovery (MOLLI) T1 relaxation image (arrow). E. Representative axial intravoxel incoherent motion diffusion-weighted images with increasing b-values (left to right, arrows). Figure 2 Variation in circulating and imaging biomarkers in Crohn’s disease patients with medical and surgical management. Ctrl: non-IBD healthy controls; Med: CD patients with nonsurgical medical management; Surg: CD patients with surgical management.

Clinical Value and Reliability of Quantitative Assessments of Lumbosacral Nerve Root Using Diffusion Tensor and Diffusion Weighted MR Imaging: A Systematic Review.

Lumbosacral radicular pain diagnosis remains challenging. Diffusion tensor imaging (DTI) and diffusion weighted imaging (DWI) have potential to quantitatively evaluate symptomatic nerve root, which may facilitate diagnosis. To determine the ability of DTI and DWI metrics, namely fractional anisotropy (FA) and apparent diffusion coefficient (ADC), to discriminate between healthy and symptomatic lumbosacral nerve roots, to evaluate the association between FA and ADC values and patient symptoms, and to determine FA and ADC reliability. Systematic review. Eight hundred twelve patients with radicular pain with or without radiculopathy caused by musculoskeletal-related compression or inflammation of a single, unilateral lumbosacral nerve root and 244 healthy controls from 29 studies. Diffusion weighted echo planar imaging sequence at 1.5 T or 3 T. An extensive systematic review of the literature was conducted in Embase, Scopus, and Medline databases. FA and ADC values in symptomatic and contralateral lumbosacral nerve roots were extracted and summarized, together with intra- and inter-rater agreements. Where available, associations between DWI or DTI parameters and patient symptoms or symptom duration were extracted. The main results of the included studies are summarized. No additional statistical analyses were performed. The DTI studies systematically found significant differences in FA values between the symptomatic and contralateral lumbosacral nerve root of patients suffering from radicular pain with or without radiculopathy. In contrast, identification of the symptomatic nerve root with ADC values was inconsistent for both DTI and DWI studies. FA values were moderately to strongly correlated with several symptoms (eg, disability, nerve dysfunction, and symptom duration). The inter- and intra-rater reliability of DTI parameters were moderate to excellent. The methodological quality of included studies was very heterogeneous. This systematic review showed that DTI was a reliable and discriminative imaging technique for the assessment of symptomatic lumbosacral nerve root, which more consistently identified the symptomatic nerve root than DWI. Further studies of high quality are needed to confirm these results. N/A TECHNICAL EFFICACY: Stage 2.

Sleep Patterns and Prospective Diffusion Weighted Imaging Biomarkers: the Sleep and Dementia Consortium (SDC)

AbstractBackgroundAdequate sleep is necessary to maintain brain health, with sleep disturbances associated with higher Alzheimer’s disease (AD) risk. Diffusion‐weighted imaging (DWI) metrics are increasingly recognized as useful neuroimaging biomarkers to detect AD‐related white matter degeneration. We assessed the relationship between sleep patterns and prospective DWI metrics in the Sleep and Dementia Consortium (SDC). The SDC studies associations between polysomnography (PSG)‐derived sleep with dementia risk and cognitive and MRI endophenotypes.MethodThe SDC includes five community‐based cohorts, two of which have DWI acquisitions: The Framingham Heart Study (FHS) and the Atherosclerosis Risk in Communities study (ARIC). Dementia‐free participants who underwent both PSG and DWI‐MRI were selected, including 354 FHS participants (56.6±7.1y, 57%W), and 184 ARIC participants (61.6±5.0y, 52%W). The MRI session was approximately 15 years after the PSG on average (FHS:17.0±1.3y; ARIC:15.8±0.8y). Fractional anisotropy (FA) and mean diffusivity (MD) were considered for both cohorts, in addition to free‐water (FW) in the FHS. Sleep metrics were harmonized centrally, distributed for cohort‐specific linear regressions, and study‐level estimates were pooled in random effects meta‐analyses. Analyses were adjusted for demographics, obesity, time between PSG and MRI, antidepressants and sedative medication usage. An interaction term by APOE4 allele carrier status in regression models was used to test its moderating effect.ResultIn the FHS, sleep fragmentation was associated with DWI measures in the expected direction: Higher Wake After Sleep Onset and lower Sleep Maintenance Efficiency were associated with lower FA (β±SE = ‐0.17±0.09,p = 0.04; β±SE = 0.23±0.10,p = 0.03), higher MD (β±SE = 0.15±0.07,p = 0.04; β±SE = ‐0.20±0.09,p = 0.03), and higher FW (β±SE = 0.17±0.07,p = 0.02; β±SE = ‐0.22±0.08,p = 0.008). Meta‐analysis of FHS and ARIC revealed significant pooled effects between lower Sleep Maintenance Efficiency and lower FA (β±SE = 0.17±0.08,p = 0.04). In the FHS, APOE4 allele significantly moderated the association between REM sleep proportion with FA and MD, where lower REM sleep percentage was associated with higher MD (β±SE = ‐4.89±1.95,p = 0.02) and lower FA (β±SE = 4.93±2.26,p = 0.03) in APOE4 carriers only.ConclusionIn the SDC, sleep fragmentation was associated with MRI markers of poorer white matter integrity 15 years later. Less REM sleep was associated with poorer white matter integrity in APOE4 allele carriers only, suggesting that disrupted sleep architecture may contribute and interact with neurodegenerative processes to affect brain integrity.

Childhood development of brain white matter myelin: a longitudinal T1w/T2w-ratio study

Myelination of human brain white matter (WM) continues into adulthood following birth, facilitating connection within and between brain networks. In vivo MRI studies using diffusion weighted imaging (DWI) suggest microstructural properties of brain WM increase over childhood and adolescence. Although DWI metrics, such as fractional anisotropy (FA), could reflect axonal myelination, they are not specific to myelin and could also represent other elements of WM microstructure, for example, fibre architecture, axon diameter and cell swelling. Little work exists specifically examining myelin development. The T1w/T2w ratio approach offers an alternative non-invasive method of estimating brain myelin. The approach uses MRI scans that are routinely part of clinical imaging and only require short acquisition times. Using T1w/T2w ratio maps from three waves of the Neuroimaging of the Children’s Attention Project (NICAP) [N = 95 (208 scans); 44% female; ages 9.5–14.20 years] we aimed to investigate the developmental trajectories of brain white matter myelin in children as they enter adolescence. We also aimed to investigate whether longitudinal changes in myelination of brain WM differs between biological sex. Longitudinal regression modelling suggested non-linear increases in WM myelin brain wide. A positive parabolic, or U-shaped developmental trajectory was seen across 69 of 71 WM tracts modelled. At a corrected level, no significant effect for sex was found. These findings build on previous brain development research by suggesting that increases in brain WM microstructure from childhood to adolescence could be attributed to increases in myelin.

The role and potential of using quantitative MRI biomarkers for imaging guidance in brain cancer radiotherapy treatment planning: A systematic review.

Improving the accuracy of brain tumour radiotherapy (RT) treatment planning is important to optimise patient outcomes. This systematic review investigates primary studies providing clinical evidence for the integration of quantitative magnetic resonance imaging (qMRI) biomarkers and MRI radiomics to optimise brain tumour RT planning. PubMed, Scopus, Embase and Web of Science databases were searched for all years until June 21, 2022. The search identified original articles demonstrating clinical evidence for the use of qMRI biomarkers and MRI radiomics for the optimization of brain cancer RT planning. Relevant information was extracted and tabulated, including qMRI metrics and techniques, impact on RT plan optimization and changes in target and normal tissue contouring and dose distribution. Nineteen articles met the inclusion criteria. Studies were grouped according to the qMRI biomarkers into: 1) diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI; five studies); 2) diffusion tensor imaging (DTI; seven studies); and 3) MR spectroscopic imaging (MRSI; seven studies). No relevant MRI-based radiomics studies were identified. Integration of DTI maps offers the potential for improved organs at risk (OAR) sparing. MRSI metabolic maps are a promising technique for improving delineation accuracy in terms of heterogeneity and infiltration, with OAR sparing. No firm conclusions could be drawn regarding the integration of DWI metrics and PWI maps. Integration of qMRI metrics into RT planning offers the potential to improve delineation and OAR sparing. Clinical trials and consensus guidelines are required to demonstrate the clinical benefits of such approaches.

Impact of chronic exposure to legacy environmental contaminants on the corpus callosum microstructure: A diffusion MRI study of Inuit adolescents

Exposure to environmental contaminants is an important public health concern for the Inuit population of northern Québec, who have been exposed to mercury (Hg), polychlorinated biphenyls (PCBs) and lead (Pb). During the last 25 years, the Nunavik Child Development Study (NCDS) birth cohort has reported adverse associations between these exposures and brain function outcomes. In the current study, we aimed to determine whether contaminant exposure is associated with alterations of the corpus callosum (CC), which plays an important role in various cognitive, motor and sensory function processes. Magnetic resonance imaging (MRI) was administered to 89 NCDS participants (mean age ± SD = 18.4 ± 1.2). Diffusion-weighted imaging was assessed to characterize the microstructure of the CC white matter in 7 structurally and functionally distinct regions of interest (ROIs) using a tractography-based segmentation approach. The following metrics were computed: fiber tract density, fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD). Multiple linear regression models adjusted for sex, age, current alcohol/drug use and fish nutrients (omega-3 fatty acids and selenium) were conducted to assess the association between diffusion-weighted imaging metrics and Hg, PCB 153 and Pb concentrations obtained at birth in the cord blood and postnatally (mean values from blood samples at 11 and 18 years of age). Exposures were not associated with fiber tract density. Nor were significant associations found with cord and postnatal blood Pb concentrations for FA. However, pre- and postnatal Hg and PCB concentrations were significantly associated with higher FA of several regions of the CC, namely anterior midbody, posterior midbody, isthmus, and splenium, with the most pronounced effects observed in the splenium. FA results were mainly associated with lower RD. This study shows that exposure to Hg and PCB 153 alters the posterior microstructure of the CC, providing neuroimaging evidence of how developmental exposure to environmental chemicals can impair brain function and behavior in late adolescence.

Performance of apparent diffusion coefficient values and ratios for the prediction of prostate cancer aggressiveness across different MRI acquisition settings.

In this study, we assessed the performance of apparent diffusion coefficient (ADC) and diffusion-weighted imaging (DWI) metrics and their ratios across different magnetic resonance imaging (MRI) acquisition settings, with or without an endorectal coil (ERC), for the evaluation of prostate cancer (PCa) aggressiveness using whole-mount specimens as a reference. We retrospectively reviewed the data of prostate carcinoma patients with a Gleason score (GS) of 3+4 or higher who underwent prostate MRI using a 3T unit at our institution. They were divided into two groups based on the use of ERC for MRI acquisition, and patients who underwent prostate MRI with an ERC constituted the ERC (n = 55) data set, while the remaining patients accounted for the non-ERC data set (n = 41). DWI was performed with b-values of 50, 500, 1000, and 1,400 s/mm2, and ADC maps were automatically calculated. Additionally, computed DWI (cDWI) was performed with a b-value of 2000 s/mm2. Six ADC and two cDWI parameters were evaluated. In the ERC data set, receiver operating characteristic (ROC) curves were plotted for each metric to determine the best cutoff threshold values for differentiating GS 3+4 PCa from that with a higher GS. The performance of these cutoff values was assessed in non-ERC dataset. The diagnostic accuracies and area under the curves (AUCs) of the metrics were compared using Fisher's exact test and De Long's method, respectively. Among all metrics, the ADCmean-ratio yielded the highest AUC, 0.84, for differing GS 3+4 PCa from that with a higher GS. The best threshold cutoff values of ADCmean-ratio (£0.51) for discriminating GS 3+4 PCa from that with a higher GS classified 48 patients out of 55 with an accuracy of 87.27%. However, there was no significant difference between each metric in terms of accuracy and AUC (p = 0.163 and 0.214). Similarly, in the non-ERC data set, the ADCmean-ratio provided the highest diagnostic accuracy (82.92%) by classifying 34 patients out of 41. However, Fisher's exact test yielded no significant difference between DWI and ADC metrics in terms of diagnostic accuracy in non-ERC data (p = 0.561). The mean ADC ratio of the tumor to the normal prostate showed the highest accuracy and AUC in differentiating GS 3+4 PCa and PCa with a higher GS across different MRI acquisition settings; however, the performance of different ADC and DWI metrics did not differ significantly.

Associations between diffusion MRI microstructure and cerebrospinal fluid markers of Alzheimer's disease pathology and neurodegeneration along the Alzheimer's disease continuum.

White matter (WM) degeneration is a critical component of early Alzheimer's disease (AD) pathophysiology. Diffusion-weighted imaging (DWI) models, including diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI), and mean apparent propagator MRI (MAP-MRI), have the potential to identify early neurodegenerative WM changes associated with AD. We imaged 213 (198 cognitively unimpaired) aging adults with DWI and used tract-based spatial statistics to compare 15 DWI metrics of WM microstructure to 9 cerebrospinal fluid (CSF) markers of AD pathology and neurodegeneration treated as continuous variables. We found widespread WM injury in AD, as indexed by robust associations between DWI metrics and CSF biomarkers. MAP-MRI had more spatially diffuse relationships with Aβ42/40 and pTau, compared with NODDI and DTI. Our results suggest that WM degeneration may be more pervasive in AD than is commonly appreciated and that innovative DWI models such as MAP-MRI may provide clinically viable biomarkers of AD-related neurodegeneration in the earliest stages of AD progression.

Early and progressive dysfunction revealed by in vivo neurite imaging in the rNLS8 TDP-43 mouse model of ALS

Amyotrophic lateral sclerosis (ALS) is characterized by transactive response DNA-binding protein 43 (TDP-43) pathology, progressive loss of motor neurons and muscle dysfunction. Symptom onset can be insidious and diagnosis challenging. Conventional neuroimaging is used to exclude ALS mimics, however more advanced neuroimaging techniques may facilitate an earlier diagnosis. Here, we investigate the potential for neurite orientation dispersion and density imaging and diffusion tensor imaging (DTI) to detect microstructural changes in an experimental model of ALS with neuronal doxycycline (Dox)-suppressible overexpression of human TDP-43 (hTDP-43). In vivo diffusion-weighted imaging (DWI) was acquired 1- and 3- weeks following the initiation of hTDP-43 expression (post-Dox) to investigate whether neurite density imaging (NDI) and orientation dispersion imaging (ODI) are affected early in this preclinical model of ALS and if so, how these metrics compare to those derived from the diffusion tensor. Tract-based spatial statistics at 1-week post-Dox, i.e. very early in the disease stage, demonstrated increased NDI in TDP-43 mice but no change in ODI or DTI metrics. At 3-weeks post-Dox, a reduced pattern of increased NDI was observed along with widespread increases in ODI, and decreased fractional anisotropy (FA), apparent diffusion coefficient (ADC) and axial diffusivity (AD). A hypothesis driven analysis of the bilateral corticospinal tracts demonstrated that at 1-week post-Dox, ODI was significantly increased caudally but decreased in the motor cortex of TDP-43 mice. Decreased cortical ODI had normalized by 3-weeks post-Dox and only significant increases were observed. A similar, but inverse pattern in FA was also observed. Together, these results suggest a non-monotonic relationship between DWI metrics and pathophysiological progression with TDP-43 mice exhibiting significantly altered diffusion metrics consistent with early inflammation followed by progressive axonal degeneration. Importantly, significant group-wise changes were observed in the earliest stages of disease when subtle pathology may be more elusive to traditional structural imaging techniques.

Treatment Effect of a Vascular-Disrupting Agent Dynamically Monitored by DWI: An Animal Experimental Study.

Objective To investigate the treatment effect of a vascular-disrupting agent, M410, using diffusion-weighted imaging in a rabbit model of hepatic VX2 tumor. Methods 28 New Zealand white rabbit models with VX2 liver tumors were established and were randomly divided into M410 (intravenous injection of M410 at a dose of 25 mg/kg every three days) and control (intravenous injection of saline every three days) groups. Conventional and diffusion-weighted imaging (DWI) were acquired on a 3.0 T MR unit at baseline, 4 h, d 1, d 4, d 7, and d 14 posttreatment. B-value with 700 (s/mm2) was chosen during DWI examinations. Tumor volume and apparent diffusion coefficient (ADC) values of the entire tumor and solid component of the tumor at every time point were measured. Two randomly chosen rabbits from each group were sacrificed for H&E staining and CD34 immunohistochemical assessments at each time point. An independent sample t-test was used to assess differences in tumor sizes and ADC values of the entire tumor and solid component of tumors between two groups, with P < 0.05 considered statistically significant. Result There was no significant difference in tumor volume between the two groups at baseline, 4 h, and d 1. With time, the tumors in the control group grew significantly faster than those in the M410 group, and the average ADC values of the M410 group were lower than those of the control group at d 1 and higher than those of the control group at d 4; as such, there were statistical differences between the two groups at these two time points but not at the other four time points. The following pathological results reflected the underlying morphological changes and vascular alterations. Conclusions M410 performed well in inhibiting the growth of the hepatic VX2 tumor which could be noninvasively monitored by DWI metrics.

Do contrast-enhanced and advanced MRI sequences improve diagnostic accuracy for indeterminate lipomatous tumors?

Benign, intermediate-grade and malignant tumors sometimes have overlapping imaging and clinical characteristics. The purpose of this study was to evaluate the added value of contrast-enhanced sequences (dynamic contrast enhancement (DCE)), diffusion-weighted imaging (DWI), and chemical shift imaging (CSI) to noncontrast MRI sequences for the characterization of indeterminate lipomatous tumors. Thirty-two consecutive patients with histologically proven peripheral lipomatous tumors were retrospectively evaluated. Two musculoskeletal radiologists recorded the MRI features in three sessions: (1) with noncontrast T1-weighted and fluid-sensitive sequences; (2) with addition of static pre- and post-contrast 3D volumetric T1-weighted sequences; and (3) with addition of DCE, DWI, and CSI. After each session, readers recorded a diagnosis (benign, intermediate/atypical lipomatous tumor (ALT), or malignant/dedifferentiated liposarcoma (DDL)). Categorical imaging features (presence of septations, nodules, contrast enhancement) and quantitative metrics (apparent diffusion coefficient values, CSI signal loss) were recorded. For 32 tumors, the diagnostic accuracy of both readers did not improve with the addition of contrast-enhanced sequences, DWI, or CSI (53% (17/32) session 1; 50% (16/30) session 2; 53% (17/32) session 3). Noncontrast features, including thick septations (p = 0.025) and nodules ≥1cm (p <0.001), were useful for differentiating benign tumors from ALTs and DDLs, as were DWI (p = 0.01) and CSI (p = 0.009) metrics. The addition of contrast-enhanced sequences (static, DCE), DWI, and CSI to a conventional, noncontrast MRI protocol did not improve diagnostic accuracy for differentiating benign, intermediate-grade, and malignant lipomatous tumors. However, we identified potentially useful imaging features by DCE, DWI, and CSI that may help distinguish these entities.

Study of Diffusion Weighted Imaging Derived Diffusion Parameters as Biomarkers for the Microenvironment in Gliomas

ObjectivesTo explore the efficacy of diffusion weighted imaging (DWI)-derived metrics under different models as surrogate indicators for molecular biomarkers and tumor microenvironment in gliomas.MethodsA retrospective study was performed for 41 patients with gliomas. The standard apparent diffusion coefficient (ADCst) and ADC under ultra-high b values (ADCuh) (b values: 2500 to 5000 s/mm2) were calculated based on monoexponential model. The fraction of fast diffusion (f), pseudo ADC (ADCfast) and true ADC (ADCslow) were calculated by bi-exponential model (b values: 0 to 2000 s/mm2). The apparent diffusional kurtosis (Kapp) was derived from the simplified diffusion kurtosis imaging (DKI) model (b values: 200 to 3000 s/mm2). Potential correlations between DWI parameters and immunohistological indices (i.e. Aquaporin (AQP)1, AQP4, AQP9 and Ki-67) were investigated and DWI parameters were compared between high- and low-grade gliomas, and between tumor center and peritumor. Receiver operator characteristic (ROC) curve and area under the curve (AUC) were calculated to determine the performance of independent or combined DWI parameters in grading gliomas.ResultsThe ADCslow and ADCuh at tumor center showed a stronger correlation with Ki-67 than other DWI metrics. The ADCst, ADCslow and ADCuh at tumor center presented correlations with AQP1 and AQP4 while AQP9 did not correlate with any DWI metric. Kapp showed a correlation with Ki-67 while no significant correlation with AQPs. ADCst (p < 0.001) and ADCslow (p = 0.001) were significantly lower while the ADCuh (p = 0.006) and Kapp (p = 0.005) were significantly higher in the high-grade than in the low-grade gliomas. ADCst, f, ADCfast, ADCslow, ADCuh, Kapp at the tumor center had significant differences with those in peritumor when the gliomas grade became high (p < 0.05). Involving ADCuh and Kapp simultaneously into an independent ADCst model (AUC = 0.833) could further improve the grading performance (ADCst+ADCuh+Kapp: AUC = 0.923).ConclusionDifferent DWI metrics fitted within different b-value ranges (low to ultra-high b values) have different efficacies as a surrogate indicator for molecular expression or microstructural complexity in gliomas. Further studies are needed to better explain the biological meanings of these DWI parameters in gliomas.

MR spectroscopy and diffusion imaging in people with human immunodeficiency virus: Relationships to clinical and immunologic findings.

People with human immunodeficiency virus (HIV; PWH) present a complex array of immunologic and medical disorders that impact brain structure and metabolism, complicating the interpretation of neuroimaging. This pilot study of well-characterized multi-morbid PWH examined how medical and immunologic factors predicted brain characteristics on proton MR spectroscopy (1H-MRS) and diffusion-weighted imaging (DWI). Eighteen individuals on combination antiretroviral therapy (cART), with mean age of 56 years, underwent medical history review, neuroimaging, and on the day of imaging, blood draw for assay of 20 plasma cytokines and flow cytometric characterization of peripheral blood mononuclear cell subsets. Predictors of n-acetyl aspartate, choline, myoinositol, glutamate/glutamine, fractional anisotropy and mean diffusivity were identified through bivariate correlation; those significant at p < .1000 were advanced to multivariate analysis, with models created for each neuroimaging outcome. Monocyte subsets and diverse cytokines accounted for 16 of 25 (64%) variables predicting 1H-MRS spectra in frontal gray and white matter and basal ganglia; monocyte subsets did not predict any DWI characteristic. In contrast, age, presence of hypertension, and duration of HIV infection accounted for 13 of 25 (52%) variables predicting diffusion characteristics in the corpus callosum, thalamic radiations, and basal ganglia but only 3 of 25 (12%) predictors of 1H-MRS features. 1H-MRS neurometabolites were most often predicted by immunologic factors sensitive to temporal variation, whereas DWI metrics were more often related to longer-term disease state. In multi-morbid cART-era populations, selection and interpretation of neuroimaging modalities should account for complex temporal and pathogenetic influences of immunologic abnormality, disease state, and aging.

Utility of Advanced DWI in the Detection of Spinal Cord Microstructural Alterations and Assessment of Neurologic Function in Cervical Spondylotic Myelopathy Patients.

Diffusion-weighted imaging (DWI) can quantify the microstructural changes in the spinal cord. It might be a substitute for T2 increased signal intensity (ISI) for cervical spondylotic myelopathy (CSM) evaluation and prognosis. The purpose of the study is to investigate the relationship between DWI metrics and neurologic function of patients with CSM. Retrospective. Forty-eight patients with CSM (18.8% females) and 36 healthy controls (HCs, 25.0% females). 3 T; spin-echo echo-planar imaging-DWI; turbo spin-echo T1/T2; multi-echo gradient echo T2*. For patients, conventional MRI indicators (presence and grades of T2 ISI), DWI indicators (neurite orientation dispersion and density imaging [NODDI]-derived isotropic volume fraction [ISOVF], intracellular volume fraction, and orientation dispersion index [ODI], diffusion tensor imaging [DTI]-derived fractional anisotropy [FA] and mean diffusivity [MD], and diffusion kurtosis imaging [DKI]-derived FA, MD, and mean kurtosis), clinical conditions, and modified Japanese Orthopaedic Association (mJOA) were recorded before the surgery. Neurologic function improvement was measured by the 3-month follow-up recovery rate (RR). For HCs, DWI, and mJOA were measured as baseline comparison. Continuous (categorical) variables were compared between patients and HCs using Student's t-tests or Mann-Whitney U tests (chi-square or Fisher exact tests). The relationships between DWI metrics/conventional MRI findings, and the pre-operative mJOA/RR were assessed using correlation and multivariate analysis. P < 0.05 was considered statistically significant. Among patients, grades of T2 ISI were not correlated with pre-surgical mJOA/RR (P=0.717 and0.175, respectively). NODDI ODI correlated with pre-operative mJOA (r=-0.31). DTI FA, DKI FA, and NODDI ISOVF were correlated with the recovery rate (r=0.31, 0.41, and -0.34, respectively). In multivariate analysis, NODDI ODI (DTI FA, DKI FA, NODDI ISOVF) significantly contributed to the pre-operative mJOA (RR) after adjusting for age. DTI FA, DKI FA, and NODDI ISOVF are predictors for prognosis in patients with CSM. NODDI ODI can be used to evaluate CSM severity. 3 TECHNICAL EFFICACY STAGE: 5.

White matter changes following experimental pediatric traumatic brain injury: an advanced diffusion-weighted imaging investigation.

Pediatric traumatic brain injury (pTBI) is a major community health concern. Due to ongoing maturation, injury to the brain at a young age can have devastating consequences in later life. However, how pTBI affects brain development, including white matter maturation, is still poorly understood. Here, we used advanced diffusion weighted imaging (DWI) to assess chronic white matter changes after experimental pTBI. Mice at post-natal day 21 sustained a TBI using the controlled cortical impact model and magnetic resonance imaging (MRI) was performed at 6 months post-injury using a 4.7T Bruker scanner. Four diffusion shells with 81 directions and b-values of 1000, 3000, 5000, and 7000s/mm2 were acquired and analyzed using MRtrix3 software. Advanced DWI metrics, including fiber density, fiber cross-section and a combined fiber density and cross-section measure, were investigated together with three track-weighted images (TWI): the average pathlength map, mean curvature and the track density image. These advanced metrics were compared to traditional diffusion tensor imaging (DTI) metrics which indicated that TBI injured mice had reduced fractional anisotropy and increased radial diffusivity in the white matter when compared to age-matched sham controls. Consistent with previous findings, fiber density and TWI metrics appeared to be more sensitive to white matter changes than DTI metrics, revealing widespread reductions in fiber density and TWI metrics in pTBI mice compared to sham controls. These results provide additional support for the use of advanced DWI metrics in assessing white matter degeneration following injury and highlight the chronic outcomes that can follow pTBI.

White matter microstructure and cerebrospinal fluid biomarkers of Alzheimer’s disease in middle‐aged cognitively unimpaired participants (the ALFA study)

AbstractBackgroundPrevious studies comparing white matter (WM) integrity and biomarkers of Alzheimer’s disease (AD) at early stages have yielded inconsistent results and findings have remained inconclusive. In this work, we used diffusion‐weighted imaging (DWI) and cerebrospinal fluid (CSF) biomarkers to study the relationship between neuropathological burden and neural injury in the WM in a middle‐aged cognitively unimpaired population: the ALFA+ study.MethodsN=318 cognitively unimpaired individuals from the ALFA+ study, aged from 45 to 74 (mean: 60.79∓4.66) underwent DWI and lumbar puncture. Biomarkers were measured with Elecsys® and NeuroToolKit robust prototype assays (Roche Diagnostics). Using tract‐based spatial statistics, we assessed their association with DWI metrics using individuals models including CSF markers of core AD pathology (A𝛃42, A𝛃42/40 ratio, p‐tau), neuronal injury (neurofilament light [NfL], t‐tau), synaptic dysfunction (neurogranin [NGR], 𝛂Synuclein), and inflammation (sTREM2, YKL40, GFAP, IL6, S100b). Age, sex and APOE e4 carriership were included as covariates. Supplementary analyses were performed including levels of AD core biomarkers as additional covariates and stratifying the sample into A/T groups.ResultsDWI metrics showed significant associations with A𝛃42, YKL40, IL6, NFL, NGR, pTau, tTau, S100, 𝛂Synuclein; none with GFAP, sTREM2, nor A𝛃42/40 ratio (Figures 1 and 2). Positive associations in fractional anisotropy (FA) (and negative with diffusivity) were found with A𝛃42, YKL40, NFL, NGR, S100, p‐tau and t‐tau. Negative association in FA (positive in diffusivity) was found for IL6 only. p‐tau showed the only association to be significant in both directions with FA, positive in cingular/callosal and negative in corticospinal tracts. Post‐hoc analyses on p‐tau showed significant interaction with A/T stage (Figure 3) with positive association with FA in A‐T‐ and negative in A+T+ subjects (inversely with diffusivity).ConclusionWM microstructural properties correlate in extensive regions with CSF AD core biomarkers, inflammation and axonal degeneration markers. Such associations illustrate the interplay of multiple pathways in early stages of Alzheimer’s continuum such as deleterious effects of amyloid deposition or the involvement of glial activation/inflammatory processes, resulting in observed reduced diffusivity. Furthermore, interaction with A/T stage suggest the presence of non‐monotonic dynamics occurring along the Alzheimer’s continuum.

Viscoelasticity of reward and control systems in adolescent risk taking

Heightened risk-taking tendencies during adolescence have been hypothesized to be attributable to physiological differences of maturation in key brain regions. The socioemotional system (e.g., nucleus accumbens), which is instrumental in reward response, shows a relatively earlier development trajectory than the cognitive control system (e.g., medial prefrontal cortex), which regulates impulse response. This developmental imbalance between heightened reward seeking and immature cognitive control potentially makes adolescents more susceptible to engaging in risky activities. Here, we assess brain structure in the socioemotional and cognitive control systems through viscoelastic stiffness measured with magnetic resonance elastography (MRE) and volumetry, as well as risk-taking tendencies measured using two experimental tasks in 40 adolescents (mean age ​= ​13.4 years old). MRE measures of regional brain stiffness reflect brain health and development via myelin content and glial matrix makeup, and have been shown to be highly sensitive to cognitive processes as compared to measures of regional brain volume and diffusion weighted imaging metrics. We find here that the viscoelastic and volumetric differences between the nucleus accumbens and the prefrontal cortex are correlated with increased risk-taking behavior in adolescents. These differences in development between the two brain systems can be used as an indicator of those adolescents who are more prone to real world risky activities and a useful measure for characterizing response to intervention.

Repeatability of Quantitative Diffusion-Weighted Imaging Metrics in Phantoms, Head-and-Neck and Thyroid Cancers: Preliminary Findings.

The aim of this study was to establish the repeatability measures of quantitative Gaussian and non-Gaussian diffusion metrics using diffusion-weighted imaging (DWI) data from phantoms and patients with head-and-neck and papillary thyroid cancers. The Quantitative Imaging Biomarker Alliance (QIBA) DWI phantom and a novel isotropic diffusion kurtosis imaging phantom were scanned at 3 different sites, on 1.5T and 3T magnetic resonance imaging systems, using standardized multiple b-value DWI acquisition protocol. In the clinical component of this study, a total of 60 multiple b-value DWI data sets were analyzed for test–retest, obtained from 14 patients (9 head-and-neck squamous cell carcinoma and 5 papillary thyroid cancers). Repeatability of quantitative DWI measurements was assessed by within-subject coefficient of variation (wCV%) and Bland–Altman analysis. In isotropic diffusion kurtosis imaging phantom vial with 2% ceteryl alcohol and behentrimonium chloride solution, the mean apparent diffusion (Dapp × 10−3 mm2/s) and kurtosis (Kapp, unitless) coefficient values were 1.02 and 1.68 respectively, capturing in vivo tumor cellularity and tissue microstructure. For the same vial, Dapp and Kapp mean wCVs (%) were ≤1.41% and ≤0.43% for 1.5T and 3T across 3 sites. For pretreatment head-and-neck squamous cell carcinoma, apparent diffusion coefficient, D, D*, K, and f mean wCVs (%) were 2.38%, 3.55%, 3.88%, 8.0%, and 9.92%, respectively; wCVs exhibited a higher trend for papillary thyroid cancers. Knowledge of technical precision and bias of quantitative imaging metrics enables investigators to properly design and power clinical trials and better discern between measurement variability versus biological change.