Quantitative MRI Measures Research Articles

Author Response: Prospective Natural History Study in 24 Adult Patients With LGMDR12 Over 2 Years of Follow-up: Quantitative MRI and Clinical Outcome Measures.

We read with interest the comments by Professor Kawada on our article.1 As described in the article, all participants were evaluated 3 times within strict 1-year intervals; there were no missed visits or missing data. Furthermore, we defined disease onset as the start of clinical symptoms of limb-girdle muscular dystrophy autosomal recessive type 12 (LGMDR12) and thereby excluded patients with isolated hyperCKemia for increased phenotypic homogeneity.

Reader Response: Prospective Natural History Study in 24 Adult Patients With LGMDR12 Over 2 Years of Follow-up: Quantitative MRI and Clinical Outcome Measures.

De Wel et al. conducted a prospective study to evaluate prognosis in 24 patients with limb-girdle muscular dystrophy autosomal recessive type 12 (LGMDR12).1 They prepared 24 healthy controls by way of an age- and sex-matching procedure. Biodex(R) isometric dynamometry showed a significant decrease of muscle strength in the right quadricep muscles for all patients after 1 year. In contrast, outcomes from the 6-minute walk distance, 10-meter walk test, and Medical Research Council sum scores did not change significantly, even after 2 years. The authors recognized that thigh muscle proton density fat fraction imaging was a sensitive indicator to track progressive muscle fat replacement.

Microstructural mapping of dentate gyrus pathology in Alzheimer’s disease: A 16.4 Tesla MRI study

The dentate gyrus (DG) is an integral portion of the hippocampal formation, and it is composed of three layers. Quantitative magnetic resonance (MR) imaging has the capability to map brain tissue microstructural properties which can be exploited to investigate neurodegeneration in Alzheimer’s disease (AD). However, assessing subtle pathological changes within layers requires high resolution imaging and histological validation. In this study, we utilized a 16.4 Tesla scanner to acquire ex vivo multi-parameter quantitative MRI measures in human specimens across the layers of the DG. Using quantitative diffusion tensor imaging (DTI) and multi-parameter MR measurements acquired from AD (N = 4) and cognitively normal control (N = 6) tissues, we performed correlation analyses with histological measurements. Here, we found that quantitative MRI measures were significantly correlated with neurofilament and phosphorylated Tau density, suggesting sensitivity to layer-specific changes in the DG of AD tissues.

Multimodal-neuroimaging machine-learning analysis of motor disability in multiple sclerosis.

Motor disability is a dominant and restricting symptom in multiple sclerosis, yet its neuroimaging correlates are not fully understood. We apply statistical and machine learning techniques on multimodal neuroimaging data to discriminate between multiple sclerosis patients and healthy controls and to predict motor disability scores in the patients. We examine the data of sixty-four multiple sclerosis patients and sixty-five controls, who underwent the MRI examination and the evaluation of motor disability scales. The modalities used comprised regional fractional anisotropy, regional grey matter volumes, and functional connectivity. For analysis, we employ two approaches: high-dimensional support vector machines run on features selected by Fisher Score (aiming for maximal classification accuracy), and low-dimensional logistic regression on the principal components of data (aiming for increased interpretability). We apply analogous regression methods to predict symptom severity. While fractional anisotropy provides the classification accuracy of 96.1% and 89.9% with both approaches respectively, including other modalities did not bring further improvement. Concerning the prediction of motor impairment, the low-dimensional approach performed more reliably. The first grey matter volume component was significantly correlated (R = 0.28-0.46, p < 0.05) with most clinical scales. In summary, we identified the relationship between both white and grey matter changes and motor impairment in multiple sclerosis. Furthermore, we were able to achieve the highest classification accuracy based on quantitative MRI measures of tissue integrity between patients and controls yet reported, while also providing a low-dimensional classification approach with comparable results, paving the way to interpretable machine learning models of brain changes in multiple sclerosis.

NIMG-48. MULTI-ECHO SPIN-AND-GRADIENT ECHO (SAGE) PERFUSION MRI TO EVALUATE BRAIN TUMOR MICROSTRUCTURE AND MICROVASCULATURE

Abstract BACKGROUND In a classic DSC perfusion sequence, T1 and T2* leakage effects compete in determining the post-bolus signal, and are influenced by tissue geometry (i.e. cell density, cell size). Different DSC sequences can be variously influenced by these effects, depending on the different degree of T1 weighting and the pre-bolus administration. Multi-echo spin-and-gradient echo (SAGE) perfusion MRI enables to disentangle T2* and T1 components that contribute to the classic DSC curve, and to simultaneously compute DSC and DCE perfusion metrics. METHODS We retrospectively selected patients with: diagnosis of primary brain tumor, availability of SAGE-based DSC perfusion and DWI datasets, availability of histopathological images from targeted biopsies located within contrast-enhancing tissue. Post-processing allowed to distinguish the pure T2* component from the pure T1 component, and to perform a DCE analysis on the latter. Quantitative perfusion MRI measurements were then evaluated with respect to underlying histopathology. RESULTS Histopathological images were available for 22 targeted biopsies (across 10 patients) meeting the inclusion criteria. The following novel MRI quantitative maps were successfully computed voxelwise: ΔR2* at steady state (reflecting T2* leakage effects), ΔR1 at steady state (reflecting T1 leakage effects), transverse relaxivity at tracer equilibrium (TRATE, reflecting the combination of T2* and T1 leakage effects). In addition, Ve and ktrans were computed from the DCE analysis, and the percentage of signal recovery (PSR) was computed from the second echo of the multi-echo DSC (comparable to a classic single-echo DSC sequence). CONCLUSIONS Histopathological validation will assess the usefulness of these novel multi-echo derived quantitative maps for the non-invasive prediction of tumor microstructure. This would be particularly relevant for: 1) differential diagnosis between brain tumors with different cell size and cell density (e.g. lymphoma vs glioblastoma); 2) treatment response assessment (as pre-existing studies proved that cell shrinkage is an early event in treatment response).

Impact of COVID-19 Related Maternal Stress on Fetal Brain Development: A Multimodal MRI Study.

Disruptions in perinatal care and support due to the COVID-19 pandemic was an unprecedented but significant stressor among pregnant women. Various neurostructural differences have been re-ported among fetuses and infants born during the pandemic compared to pre-pandemic counterparts. The relationship between maternal stress due to pandemic related disruptions and fetal brain is yet unexamined. Pregnant participants with healthy pregnancies were prospectively recruited in 2020-2022 in the greater Los Angeles Area. Participants completed multiple self-report assessments for experiences of pandemic related disruptions, perceived stress, and coping behaviors and underwent fetal MRI. Maternal perceived stress exposures were correlated with quantitative multimodal MRI measures of fetal brain development using multivariate models. Increased maternal perception of pandemic related stress positively correlated with normalized fetal brainstem volume (suggesting accelerated brainstem maturation). In contrast, increased maternal perception of pandemic related stress correlated with reduced global fetal brain temporal functional variance (suggesting reduced functional connectivity). We report alterations in fetal brainstem structure and global functional fetal brain activity associated with increased maternal stress due to pandemic related disruptions, suggesting altered fetal programming. Long term follow-up studies are required to better understand the sequalae of these early multi-modal brain disruptions among infants born during the COVID-19 pandemic.

Spatial Gradients of Quantitative MRI as Biomarkers for Early Detection of Osteoarthritis: Data From Human Explants and the Osteoarthritis Initiative.

Healthy articular cartilage presents structural gradients defined by distinct zonal patterns through the thickness, which may be disrupted in the pathogenesis of several disorders. Analysis of textural patterns using quantitative MRI data may identify structural gradients of healthy or degenerating tissue that correlate with early osteoarthritis (OA). To quantify spatial gradients and patterns in MRI data, and to probe new candidate biomarkers for early severity of OA. Retrospective study. Fourteen volunteers receiving total knee replacement surgery (eight males/two females/four unknown, average age ± standard deviation: 68.1 ± 9.6 years) and 10 patients from the OA Initiative (OAI) with radiographic OA onset (two males/eight females, average age ± standard deviation: 57.7 ± 9.4 years; initial Kellgren-Lawrence [KL] grade: 0; final KL grade: 3 over the 10-year study). 3.0-T and 14.1-T, biomechanics-based displacement-encoded imaging, fast spin echo, multi-slice multi-echo T2 mapping. We studied structure and strain in cartilage explants from volunteers receiving total knee replacement, or structure in cartilage of OAI patients with progressive OA. We calculated spatial gradients of quantitative MRI measures (eg, T2) normal to the cartilage surface to enhance zonal variations. We compared gradient values against histologically OA severity, conventional relaxometry, and/or KL grades. Multiparametric linear regression for evaluation of the relationship between residuals of the mixed effects models and histologically determined OA severity scoring, with a significance threshold at α=0.05. Gradients of individual relaxometry and biomechanics measures significantly correlated with OA severity, outperforming conventional relaxometry and strain metrics. In human explants, analysis of spatial gradients provided the strongest relationship to OA severity (R2 =0.627). Spatial gradients of T2 from OAI data identified variations in radiographic (KL Grade 2) OA severity in single subjects, while conventional T2 alone did not. Spatial gradients of quantitative MRI data may improve the predictive power of noninvasive imaging for early-stage degeneration. 1 TECHNICAL EFFICACY: Stage 1.

Association of lumbar vertebral bone marrow and paraspinal muscle fat composition with intervertebral disc degeneration: 3T quantitative MRI findings from the population-based KORA study

ObjectiveTo assess the association of lumbar bone marrow adipose tissue fat fraction (BMAT-FF) and paraspinal muscle proton density fat fraction (PDFF) and their interplay with intervertebral disc degeneration (IVDD).MethodsIn this retrospective cross-sectional study based on a prospective population-based cohort, BMAT-FF and PDFF of asymptomatic individuals were calculated based on 3T-MRI dual-echo and multi-echo Dixon VIBE sequences. IVDD was assessed at motion segments L1 to L5 and dichotomized based on Pfirrmann grade ≥ 4 and/or presence of other severe degenerative changes or spinal abnormalities at least at one segment. Pearson’s correlation coefficients were calculated for BMAT-FF and PDFF. Univariable and multivariable logistic regression models for IVDD were calculated.ResultsAmong 335 participants (mean age: 56.2 ± 9.0 years, 43.3% female), the average BMI was 27.7 ± 4.5 kg/m2 and the prevalence of IVDD was high (69.9%). BMAT-FF and PDFF were significantly correlated (r = 0.31–0.34; p < 0.001). The risk for IVDD increased with higher PDFF (OR = 1.45; CI 1.03, 2.04) and BMAT-FF (OR = 1.56; CI 1.16, 2.11). Pairwise combinations of PDFF and BMAT-FF quartiles revealed a lower risk for IVDD in individuals in the lowest BMAT-FF and PDFF quartile (OR = 0.21; CI 0.1, 0.48). Individuals in the highest BMAT-FF and PDFF quartile showed an increased risk for IVDD (OR = 5.12; CI 1.17, 22.34)ConclusionLumbar BMAT-FF and paraspinal muscle PDFF are correlated and represent both independent and additive risk factors for IVDD. Quantitative MRI measurements of paraspinal myosteatosis and vertebral bone marrow fatty infiltration may serve as imaging biomarkers to assess the individual risk for IVDD.Key Points• Fat composition of the lumbar vertebral bone marrow is positively correlated with paraspinal skeletal muscle fat.• Higher fat-fractions of lumbar vertebral bone marrow and paraspinal muscle are both independent as well as additive risk factors for intervertebral disc degeneration.• Quantitative magnetic resonance imaging measurements of bone marrow and paraspinal muscle may serve as imaging biomarkers for intervertebral disc degeneration.

Spatial profiles provide sensitive MRI measures of the midbrain micro- and macrostructure

The midbrain is the rostral-most part of the brainstem. It contains numerous nuclei and white matter tracts, which are involved in motor, auditory and visual processing, and changes in their structure and function have been associated with aging, as well as neurodegenerative disorders. Current tools for estimating midbrain subregions and their structure with MRI require high resolution and multi-parametric quantitative MRI measures. We propose an approach that relies on morphology to calculate profiles along the midbrain and show these profiles are sensitive to the underlying macrostructure of the midbrain.First, we show that the midbrain structure can be sampled, within subject space, along three main axes of the left and right midbrain, producing profiles that are similar across subjects. We use two data sets with different field strengths, that contain R1, R2* and QSM maps and show that the profiles are highly correlated both across subjects and between datasets. Next, we compare profiles of the midbrain that sample ROIs, and show that the profiles along the first two axes sample the midbrain in a way that reliably separates the main structures, i.e., the substantia nigra, the red nucleus, and periaqueductal gray. We further show that age differences which are localized to specific nuclei, are reflected in the profiles. Finally, we generalize the same approach to calculate midbrain profiles on a third clinically relevant dataset using HCP subjects, with metrics such as the diffusion tensor and semi-quantitative data such as T1w/T2w maps.Our results suggest that midbrain profiles, both of quantitative and semi-quantitative estimates are sensitive to the underlying macrostructure of the midbrain. The midbrain profiles are calculated in native space, and rely on simple measurements. We show that it is robust and can be easily expanded to different datasets, and as such we hope that it will be of great use to the community and to the study of the midbrain in particular.

Quantitative spinal cord MRI and sexual dysfunction in multiple sclerosis.

BackgroundSexual dysfunction (SD) is frequently reported in multiple sclerosis (MS) and is likely related to MS-related damage to the spinal cord (SC).ObjectiveTo assess associations between SD and quantitative MRI measures in people with MS (pwMS).MethodsThis pilot study included 17 pwMS with SD who completed questionnaires assessing SD, mood, and fatigue. All participants underwent brain, cervical, and thoracic SC-MRI at 3T. Quantitative brain and SC-MRI measures, including brain/SC atrophy, SC lesion count, diffusion-tensor imaging (DTI) indices (fractional anisotropy [FA], mean, perpendicular, parallel diffusivity [MD, λ⊥, λ||]) and magnetization-transfer ratio (MTR) were obtained. Associations between quantitative MRI measures and SD were assessed while controlling for the extent of mood and fatigue symptomatology.ResultsSubjects were a mean age of 46.9 years and 29% female. All subjects had self-reported SD (MSISQ-19 = 40.7, SQoL: 55.9) and 65% had a concurrent psychiatric diagnosis. When correlations between SD severity were assessed with individual brain and SC-MRI measures while controlling for psychiatric symptomatology, no associations were found. The only variables showing independent associations with SD were anxiety (p = 0.03), depression (p = 0.05), and fatigue (p = 0.04).ConclusionWe found no correlations between quantitative MRI measures in the brain and SC and severity of SD in pwMS, but psychiatric symptomatology and fatigue severity demonstrated relationships with SD. The multifactorial nature of SD in pwMS mandates a multidisciplinary approach.

Quantitative RECIST derived from multiparametric MRI in evaluating response of esophageal squamous cell carcinoma to neoadjuvant therapy.

To develop a quantitative Response Evaluation Criteria in Solid Tumors (qRECIST) for evaluating response to neoadjuvant therapy (nT) in ESCCs relying on multiparametric (mp) MRI. Patients with cT2-T4a/N0-N3/M0 ESCC undergoing pre-nT and post-nT esophageal mpMRI before radical resection were prospectively included. Images were reviewed by two experienced radiologists. qRECIST was redefined using four methods including conventional criterion (cRECIST) and three model-dependent RECIST relying on quantitative MRI measurements at pre-nT, post-nT, and delta pre-post nT, respectively. Pathological tumor regression grades (TRGs) were used as a reference standard. The rates of agreement between four qRECIST methods and TRGs were determined with a Cronbach's alpha test, area under the curve (AUC), and a diagnostic odds ratio meta-analysis. Ninety-one patients were enrolled. All four methods revealed high inter-reader agreements between the two radiologists, with a Kappa coefficient of 0.96, 0.87, 0.88, and 0.97 for cRECIST, pre-nT RECIST, post-nT RECIST, and delta RECIST, respectively. Among them, delta RECIST achieved the highest overall agreement rate (67.0% [61/91]) with TRGs, followed by post-nT RECIST (63.8% [58/91]), cRECIST (61.5% [56/91]), and pre-nT RECIST (36.3% [33/91]). Especially, delta RECIST achieved the highest accuracy (97.8% [89/91]) in distinguishing responders from non-responders, with 97.3% (34/35) for responders and 98.2% (55/56) for non-responders. Post-nT RECIST achieved the highest accuracy (93.4% [85/91]) in distinguishing complete responders from non-pCRs, with 77.8% (11/18) for pCRs and 94.5% (69/73) for non-pCRs. The qRECIST with mpMRI can assess treatment-induced changes and may be used for early prediction of response to nT in ESCC patients. • Quantitative mpMRI can reliably assess tumor response, and delta RECIST modelhad the best performance in evaluating response to nT in ESCCs,withan AUC of 0.98, 0.95, 0.80, and 0.82 for predicting TRG0, TRG1, TRG2, and TRG3, respectively. • In distinguishing responders from non-responders, the rate of agreement between delta RECIST and pathology was 97.3% (34/35) for responders and 98.2% (55/56) for non-responders, resulting in an overall agreement rate of 97.8% (89/91). • In distinguishing pCRs from non-pCR, the rate of agreement between MRI and pathology was 77.8% (11/18) for pCRs and 94.5% (69/73) for non- pCRs, resulting in an overall agreement rate of 91.2% (83/91).

Using quantitative MRI to study the association of isocitrate dehydrogenase (IDH) status with oxygen metabolism and cellular structure changes in glioma

ObjectiveTo investigate the characteristics of oxygen metabolism and the cellular structure of glioma using quantitative MRI to predict the isocitrate dehydrogenase 1 (IDH1) status and to further understand the biological characteristics of gliomas. MethodsIn this retrospective study, 94 patients with gliomas eventually received quantitative MRI measures to study oxygen metabolism. The oxygen metabolism biomarker maps (oxygen extraction fraction [OEF] and cerebral metabolic rate of oxygen [CMRO2]) and the tissue-cellular-specific (R2t*) MRI relaxation parameter were evaluated in different regions of glioma. ResultsMRI results showed differences in oxygen metabolism measures in all patients with gliomas of different IDH1 statuses. Compared to patients with IDH1 mutant gliomas, patients with IDH1 wild type gliomas showed increased (P < 0.01) CMRO2, OEF, cerebral blood volume [CBF], and R2t* measures in tumor regions, while only OEF, CBF and R2t* were found to be increased (P < 0.05) in the peritumoral area. OEF achieved the best performance for distinguishing IDH1 wild type and mutant gliomas in the tumor area (AUC = 0.732, P < 0.001). R2t* values correlated with Ki-67(R = 0.35, P < 0.001) in the tumor area, while no significant correlations between Ki-67 and R2t* were found in the peritumoral area (R = 0.19, P = 0.072). ConclusionQuantitative MRI has potential applications in studying the tumor and peritumoral areas of glioma, and it has the ability to predict and reveal the characteristics of oxygen metabolism and cellular structure in different regions of gliomas.

Longitudinal Changes in MRI Muscle Morphometry and Composition in People With Inclusion Body Myositis.

Limited data suggest that quantitative MRI (qMRI) measures have potential to be used as trial outcome measures in sporadic inclusion body myositis (sIBM) and as a noninvasive assessment tool to study sIBM muscle pathologic processes. Our aim was to evaluate changes in muscle structure and composition using a comprehensive multiparameter set of qMRI measures and to assess construct validity and responsiveness of qMRI measures in people with sIBM. This was a prospective observational cohort study with assessments at baseline (n = 30) and 1 year (n = 26). qMRI assessments include thigh muscle volume (TMV), inter/intramuscular adipose tissue (IMAT), muscle fat fraction (FF), muscle inflammation (T2 relaxation time), IMAT from T2* relaxation (T2*-IMAT), intermuscular connective tissue from T2* relaxation (T2*-IMCT), and muscle macromolecular structure from the magnetization transfer ratio (MTR). Physical performance assessments include sIBM Physical Functioning Assessment (sIFA), 6-minute walk distance, and quantitative muscle testing of the quadriceps. Correlations were assessed using the Spearman correlation coefficient. Responsiveness was assessed using the standardized response mean (SRM). After 1 year, we observed a reduction in TMV (6.8%, p < 0.001) and muscle T2 (6.7%, p = 0.035), an increase in IMAT (9.7%, p < 0.001), FF (11.2%, p = 0.030), connective tissue (22%, p = 0.995), and T2*-IMAT (24%, p < 0.001), and alteration in muscle macromolecular structure (ΔMTR = -26%, p = 0.002). A decrease in muscle T2 correlated with an increase in T2*-IMAT (r = -0.47, p = 0.008). Deposition of connective tissue and IMAT correlated with deterioration in sIFA (r = 0.38, p = 0.032; r = 0.34, p = 0.048; respectively), whereas a decrease in TMV correlated with a decrease in quantitative muscle testing (r = 0.36, p = 0.035). The most responsive qMRI measures were T2*-IMAT (SRM = 1.50), TMV (SRM = -1.23), IMAT (SRM = 1.20), MTR (SRM = -0.83), and T2 relaxation time (SRM = -0.65). Progressive deterioration in muscle quality measured by qMRI is associated with a decline in physical performance. Inflammation may play a role in triggering fat infiltration into muscle. qMRI provides valid and responsive measures that might prove valuable in sIBM experimental trials and assessment of muscle pathologic processes. This study provides Class I evidence that qMRI outcome measures are associated with physical performance measures in patients with sIBM.

Comparison of Quantitative Liver US and MRI in Patients with Liver Disease.

Background Quantitative US techniques can be used to identify changes of liver disease, but data regarding their diagnostic performance and relationship to MRI measures are sparse. Purpose To define associations between quantitative US and MRI measures of the liver in children, adolescents, and young adults with liver disease and to define the predictive ability of quantitative US measures to detect abnormal liver stiffening and steatosis defined with MRI. Materials and Methods In this prospective study, consecutive patients aged 8-21 years and known to have or suspected of having liver disease and body mass index less than 35 kg/m2 underwent 1.5-T MRI and quantitative liver US during the same visit at a pediatric academic medical center between April 2018 and December 2020. Acquired US parameters included shear-wave speed (SWS) and attenuation coefficient, among others. US parameters were compared with liver MR elastography and liver MRI proton density fat fraction (PDFF). Pearson correlation, multiple logistic regression, and receiver operating characteristic curve analyses were performed to assess associations and determine the performance of US relative to that of MRI. Results A total of 44 study participants (mean age, 16 years ± 4 [SD]; age range, 8-21 years; 23 male participants) were evaluated. There was a positive correlation between US SWS and MR elastography stiffness (r = 0.73, P < .001). US attenuation was positively correlated with MRI PDFF (r = 0.45, P = .001). For the prediction of abnormal (>2.8 kPa) liver shear stiffness, SWS (1.56 m/sec [7.3 kPa] cutoff) had an area under the receiver operating characteristic curve (AUC) of 0.95 with 91% sensitivity (95% CI: 71, 99) (20 of 22 participants) and 95% specificity (95% CI: 76, 99) (20 of 21 participants). For the prediction of abnormal (>5%) liver PDFF, US attenuation (0.55 dB/cm/MHz cutoff) had an AUC of 0.75 with a sensitivity of 73% (95% CI: 39, 94) (eight of 11 participants) and a specificity of 73% (95% CI: 55, 86) (24 of 33 participants). Conclusion In children, adolescents, and young adults with known or suspected liver disease, there was moderate to high correlation between US shear-wave speed (SWS) and MR elastography-derived stiffness. US SWS predicted an abnormal liver shear stiffness with high performance. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Khanna and Alazraki in this issue.

Prospective Natural History Study in 24 Adult Patients With LGMDR12 Over 2 Years of Follow-up: Quantitative MRI and Clinical Outcome Measures.

Limb-girdle muscular dystrophy autosomal recessive type 12 (LGMDR12) is a rare hereditary muscular dystrophy for which outcome measures are currently lacking. We evaluated quantitative MRI and clinical outcome measures to track disease progression to determine which tests could be useful in future clinical trials to evaluate potential therapies. We prospectively measured the following outcome measures in all participants at baseline and after 1 and 2 years: 6-minute walk distance (6MWD), 10-meter walk test (10MWT), the Medical Research Council (MRC) sum scores, Biodex isometric dynamometry, serum creatine kinase, and 6-point Dixon MRI of the thighs. We included 24 genetically confirmed, adult patients with LGMDR12 and 24 age-matched and sex-matched healthy controls. Patients with intermediate-stage thigh muscle fat replacement at baseline (proton density fat fraction [PDFF] 20%-70%) already showed an increase in PDFF in 8 of the 14 evaluated thigh muscles after 1 year. The standardized response mean demonstrated a high responsiveness to change in PDFF for 6 individual muscles over 2 years in this group. However, in patients with early-stage (<20%) or end-stage (>70%) muscle fat replacement, PDFF did not increase significantly over 2 years of follow-up. Biodex isometric dynamometry showed a significant decrease in muscle strength in all patients in the right and left hamstrings (-6.2 Nm, p < 0.002 and -4.6 Nm, p < 0.009, respectively) and right quadriceps muscles (-9 Nm, p = 0.044) after 1 year of follow-up, whereas the 6MWD, 10MWT, and MRC sum scores were not able to detect a significant decrease in muscle function/strength even after 2 years. There was a moderately strong correlation between total thigh PDFF and clinical outcome measures at baseline. Thigh muscle PDFF imaging is a sensitive outcome measure to track progressive muscle fat replacement in selected patients with LGMDR12 even after 1 year of follow-up and correlates with clinical outcome measures. Biodex isometric dynamometry can reliably capture the loss of muscle strength over the course of 1 year in patients with LGMDR12 and should be included as an outcome measure in future clinical trials as well.

Accelerated Brain Atrophy and Changes in White Matter Diffusivity are Associated With Mortality, Declining Health, and Declining Cognitive Functioning Among Homeless and Precariously Housed Individuals: A Longitudinal Study

Individuals who are homeless or precariously housed experience poorer health and earlier mortality compared to the general population. We evaluated longitudinal changes in quantitative MRI measures of brain structure, and how these changes are related to mortality, and change in health and functioning.

The relationship between quantitative magnetic resonance imaging of the ankle plantar flexors, muscle function during walking and maximal strength in people with neuromuscular diseases

BackgroundProgression of plantar flexor weakness in neuromuscular diseases is usually monitored by muscle strength measurements, although they poorly relate to muscle function during walking. Pathophysiological changes such as intramuscular adipose tissue affect dynamic muscle function independent from isometric strength. Diffusion tensor imaging and T2 imaging are quantitative MRI measures reflecting muscular pathophysiological changes, and are therefore potential biomarkers to monitor plantar flexor functioning during walking in people with neuromuscular diseases. MethodsIn fourteen individuals with plantar flexor weakness diffusion tensor imaging and T2 scans of the plantar flexors were obtained, and the diffusion indices fractional anisotropy and mean diffusivity calculated. With a dynamometer, maximal isometric plantar flexor strength was measured. 3D gait analysis was used to assess maximal ankle moment and power during walking. FindingsFractional anisotropy, mean diffusivity and T2 relaxation time all moderately correlated with maximal plantar flexor strength (r > 0.512). Fractional anisotropy and mean diffusivity were not related with ankle moment or power (r < 0.288). T2 relaxation time was strongly related to ankle moment (r = −0.789) and ankle power (r = −0.798), and moderately related to maximal plantar flexor strength (r < 0.600). InterpretationIn conclusion, T2 relaxation time, indicative of multiple pathophysiological changes, was strongly related to plantar flexor function during walking, while fractional anisotropy and mean diffusivity, indicative of fiber size, only related to maximal plantar flexor strength. This indicates that these measures may be suitable to monitor muscle function and gain insights into the pathophysiological changes underlying a poor plantar flexor functioning during gait in people with neuromuscular diseases.

White matter myelination during early infancy is linked to spatial gradients and myelin content at birth

Development of myelin, a fatty sheath that insulates nerve fibers, is critical for brain function. Myelination during infancy has been studied with histology, but postmortem data cannot evaluate the longitudinal trajectory of white matter development. Here, we obtained longitudinal diffusion MRI and quantitative MRI measures of longitudinal relaxation rate (R1) of white matter in 0, 3 and 6 months-old human infants, and developed an automated method to identify white matter bundles and quantify their properties in each infant’s brain. We find that R1 increases from newborns to 6-months-olds in all bundles. R1 development is nonuniform: there is faster development in white matter that is less mature in newborns, and development rate increases along inferior-to-superior as well as anterior-to-posterior spatial gradients. As R1 is linearly related to myelin fraction in white matter bundles, these findings open new avenues to elucidate typical and atypical white matter myelination in early infancy.

Multimodal Investigation of Neuroinflammation in Aviremic Patients With HIV on Antiretroviral Therapy and HIV Elite Controllers.

Background and ObjectivesThe presence of HIV in the CNS has been related to chronic immune activation and cognitive dysfunction. The aim of this work was to investigate (1) the presence of neuroinflammation in aviremic people with HIV (PWH) on therapy and in nontreated aviremic PWH (elite controllers [ECs]) using a translocator protein 18 kDa radioligand; (2) the relationship between neuroinflammation and cognitive function in aviremic PWH; and (3) the relationship between [11C]-PBR28 signal and quantitative MRI (qMRI) measures of brain tissue integrity such as T1 and T2 relaxation times (rts).Methods[11C]-PBR28 (standard uptake value ratio, SUVR) images were generated in 36 participants (14 PWH, 6 ECs, and 16 healthy controls) using a statistically defined pseudoreference region. Group comparisons of [11C]-PBR28 SUVR were performed using region of interest–based and voxelwise analyses. The relationship between inflammation, qMRI measures, and cognitive function was studied.ResultsIn region of interest analyses, ECs exhibited significantly lower [11C]-PBR28 signal in the thalamus, putamen, superior temporal gyrus, prefrontal cortex, and cerebellum compared with the PWH. In voxelwise analyses, differences were observed in the thalamus, precuneus cortex, inferior temporal gyrus, occipital cortex, cerebellum, and white matter (WM). [11C]-PBR28 signal in the WM and superior temporal gyrus was related to processing speed and selective attention in PWH. In a subset of PWH (n = 12), [11C]-PBR28 signal in the thalamus and WM regions was related to a decrease in T2 rt and to an increase in T1 rt suggesting a colocalization of increased glial metabolism, decrease in microstructural integrity, and iron accumulation.DiscussionThis study casts a new light onto the role of neuroinflammation and related microstructural alterations of HIV infection in the CNS and shows that ECs suppress neuroinflammation more effectively than PWH on therapy.

Quantitative Ultrasound Assessment of Hepatic Steatosis

Non-alcoholic fatty liver disease (NAFLD) is widespread chronic disease of the live in humans withthe prevalence of 30% of the United Statespopulation.1,2 The goal of the study is to validate the performance of quantitative ultrasound algorithms in the assessment of hepatic steatosis in patients with suspected NAFLD. This prospective study enrolled a total of 31 patients with clinical suspicion of NAFLD to receive liver fat measurements by quantitative ultrasound and reference MRI measurements (proton density fat-fraction, PDFF). The following ultrasound (US) parameters based on both raw ultrasound RF (Radio Frequency) data and 2D B-mode images of the liver were analyzed with subsequent correlation with MRI-PDFF: hepatorenal index, acoustic attenuation coefficient, Nakagami coefficient parameter, shear wave viscosity, shear wave dispersion and shear wave elasticity. Ultrasound parameters were also correlated with the presence of hypertension and diabetes. The mean (± SD) age and body mass index of the patients were 49.03 (± 12.49) and 30.12 (± 6.15), respectively. Of the aforementioned ultrasound parameters, the hepatorenal index and acoustic attenuation coefficient showed a strong correlation with MRI-PDFF derivations of hepatic steatosis, with r-values of 0.829 and 0.765, respectively. None of the remaining US parameters showed strong correlations with PDFF. Significant differences in Nakagami parameters and acoustic attenuation coefficients were found in those patients with and without hypertension. Hepatorenal index and acoustic attenuation coefficient correlate well with MRI-PDFF-derived measurements of hepatic steatosis. Quantitative ultrasound is a promising tool for the diagnosis and assessment of patients with NAFLD.