MRI Assessment Research Articles

Intrinsic Brain Activity of Inferior Temporal Region Increased in Prodromal Alzheimer's Disease With Hearing Loss.

Background and ObjectiveHearing loss (HL) is one of the modifiable risk factors for Alzheimer's disease (AD). However, the underlying mechanism behind HL in AD remains elusive. A possible mechanism is cognitive load hypothesis, which postulates that over-processing of degraded auditory signals in the auditory cortex leads to deficits in other cognitive functions. Given mild cognitive impairment (MCI) is a prodromal stage of AD, untangling the association between HL and MCI might provide insights for potential mechanism behind HL.MethodsWe included 85 cognitively normal (CN) subjects with no hearing loss (NHL), 24 CN with HL, 103 mild cognitive impairment (MCI) patients with NHL, and 23 MCI with HL from the ADNI database. All subjects underwent resting-state functional MRI and neuropsychological scale assessments. Fractional amplitude of low-frequency fluctuation (fALFF) was used to reflect spontaneous brain activity. The mixed-effects analysis was applied to explore the interactive effects between HL and cognitive status (GRF corrected, voxel p-value <0.005, cluster p-value < 0.05, two-tailed). Then, the FDG data was included to further reflect the regional neuronal abnormalities. Finally, Pearson correlation analysis was performed between imaging metrics and cognitive scores to explore the clinical significance (Bonferroni corrected, p < 0.05).ResultsThe interactive effects primarily located in the left superior temporal gyrus (STG) and bilateral inferior temporal gyrus (ITG). Post-hoc analysis showed that NC with HL had lower fALFF in bilateral ITG compared to NC with NHL. NC with HL had higher fALFF in the left STG and decreased fALFF in bilateral ITG compared to MCI with HL. In addition, NC with HL had lower fALFF in the right ITG compared to MCI with NHL. Correlation analysis revealed that fALFF was associated with MMSE and ADNI-VS, while SUVR was associated with MMSE, MoCA, ADNI-EF and ADNI-Lan.ConclusionHL showed different effects on NC and MCI stages. NC had increased spontaneous brain activity in auditory cortex while decreased activity in the ITG. Such pattern altered with disease stage changing and manifested as decreased activity in auditory cortex along with increased activity in ITG in MCI. This suggested that the cognitive load hypothesis may be the underlying mechanism behind HL.

Longitudinal white matter hyperintensity changes and cognitive decline in patients with minor stroke

Background and objectiveAs reported, both minor stroke and white matter hyperintensities (WMHs) are associated with an increased risk of cognitive impairment and dementia. The underlying factors for dynamic changes in WMH volume and cognitive performances in patients with minor stroke remain poorly understood. A 2-year longitudinal study was designed to investigate the factors associated with the changes in white matter hyperintensity (WMH) volume on brain MRI and cognitive decline in patients with minor stroke.MethodsA group of eligible patients with minor ischemic stroke was recruited in a row. At the initial and 2-year follow-up visits, all the participants underwent routine examinations, multimodal MRI, and cognitive assessment. Using a lesion prediction algorithm tool, we were able to automate the measurement of the change in WMH volume. During the 2-year follow-up, cognitive function was evaluated using Telephone Interview for Cognitive Status-Modified (TICS-m). Participants’ demographic, clinical, and therapeutic data were collected and statistically analyzed. Regression analyses were used to test the relationships between risk factors and changes in WMH volume and cognitive decline.ResultsFinally, we followed up with 225/261 participants for 2 years, with a mean age of 65.67 ± 10.73 years (65.6% men). WMH volume was observed to be increased in 113 patients, decreased in 74 patients, and remained stable in 58 patients. Patients with WMH progression were more often had a history of hypertension (p = 0.006) and a higher CSVD burden both at baseline and follow-up visit (p < 0.05). Longitudinally, the proportion of patients taking antihypertension medications on a regular basis in the regression group was higher than in the stable group (p = 0.01). When compared to the stable group, the presence of lacunes (OR 9.931, 95% CI 1.597–61.77, p = 0.014) was a stronger predictor of progression in WMH volume. 87 subjects (38.6%) displayed incident cognitive impairment. The progression of WMH volume was a significant risk factor for cognitive decline (p < 0.001).ConclusionsThe longitudinal change of WMH is dynamic. The regressive WMH volume was associated with the use of antihypertensive medications on a regular basis. The presence of lacunes at the initial visit of the study was a stronger predictor of WMH progression. The progression of WMH volume could be useful in predicting cognitive decline in patients with minor stroke.

A clinical available decision support scheme for optimizing prostate biopsy based on mpMRI.

Combined MRI/Ultrasound fusion targeted biopsy (TBx) and systematic biopsy (SBx) results in better prostate cancer (PCa) detection relative to either TBx or SBx alone, while at the cost of higher number of biopsy cores and greater detection of clinically insignificant PCa. We therefore developed and evaluated a simple decision support scheme for optimizing prostate biopsy based on multiparametric (mp) MRI assessment. Total 229 patients with suspicion of PCa underwent mpMRI before combined TBx/SBx were retrospectively included. Impacts of MRI characteristics such as Prostate Imaging-Reporting and Data System (PI-RADS) score, lesion size, zonal origination, and location on biopsy performance were evaluated. A clinically available decision support scheme relying on mpMRI assessment was subsequently developed as a triage test to optimize prostate biopsy process. Cost (downgrade, upgrade, and biopsy core)-to-Effectiveness (detection rate) was systemically compared. TBx achieved comparable detection rate to combined TBx/SBx in diagnosis of PCa and clinically significant PCa (csPCa) (PCa, 59% [135/229] vs 60.7% [139/229]; csPCa, 45.9% [105/229] vs 47.2% [108/229]; p-values > 0.05) and outperformed SBx (PCa, 42.4% [97/229]; csPCa, 28.4% [65/229]; p-values < 0.001). Specially, in personalized decision support scheme, TBx accurately detected all PCa (72.5% [74/102]) in PI-RADS 5 and larger (≥1 cm) PI-RADS 3-4 observations, adding SBx to TBx only resulted in 1.4% (1/74) upgrading csPCa. For smaller (<1 cm) PI-RADS 3-4 lesions, combined TBx/SBx resulted in relatively higher detection rate (51.2% [65/127] vs 48.0% [61/127]) and lower upgrading rate (30.6% [15/49] vs 36.7% [18/49]) than TBx. The benefit of SBx added to TBx was largely restricted to smaller PI-RADS score 3-4 lesions. Using our personalized strategy of solo TBx for PI-RADS 5 and larger (≥1 cm) PI-RADS score 3-4 lesions would avoid excess SBx in 44.5% (102/229) of all biopsy-naïve patients without compromising detection rate.

Percussion test: description and diagnostic accuracy of a new manual test for bone marrow edema of the knee

BackgroundPrompt diagnosis of bone marrow lesion (BML) is difficult but critical for correct treatment. Magnetic resonance imaging is the gold standard, although expensive and time consuming. Simple and reliable clinical test for BML detection is lacking. Aim of the study is to describe a new manual clinical test called Percussion Test (PT) and to statistically determine its diagnostic accuracy in BML, compared to MRI imaging.MethodsAfter evaluation of the inclusion and exclusion criteria, 218 consecutive patients with unilateral knee pain and age comprised between 18 and 80 years old were enrolled in our observational prospective study. Informed consent was obtained for each patient. After medical history collection, PT was performed by a single operator as described. MRI was performed in the affected knee to detect the presence of BML. Coherence in PT and MRI assessment was evaluated in each quadrant of the knee via contingency tables, as sensitivity, specificity, NPV, PPV and diagnostic accuracy were calculated.ResultsNo correlation with a positive PT was demonstrated for the covariables gender (p = 0.156), age (p = 0.272) and BMI (p = 0.639).PT showed a sensitivity ranging from 60.6 (40.6–80.6) to 79.5 (63.0–96.0) and a specificity ranging from 85.7 (80.0–91.5) to 96.0 (93.1–98.9) depending on knee quadrant. Diagnostic accuracy ranged from 81.6 (75.9–86.6) to 89.4 (84.6–93.2), and p-value was < 0.00001 in a chi-squared analysis for all quadrants.ConclusionsPT showed sensitivity and specificity values that are comparable with other clinical tests routinely adopted in clinical practice. In the absence of other reliable clinical test, PT has the potential to become a useful bedside tool in the diagnosis and management of BMLs.

Comparing two artificial intelligence software packages for normative brain volumetry in memory clinic imaging.

PurposeTo compare two artificial intelligence software packages performing normative brain volumetry and explore whether they could differently impact dementia diagnostics in a clinical context.MethodsSixty patients (20 Alzheimer’s disease, 20 frontotemporal dementia, 20 mild cognitive impairment) and 20 controls were included retrospectively. One MRI per subject was processed by software packages from two proprietary manufacturers, producing two quantitative reports per subject. Two neuroradiologists assigned forced-choice diagnoses using only the normative volumetry data in these reports. They classified the volumetric profile as “normal,” or “abnormal”, and if “abnormal,” they specified the most likely dementia subtype. Differences between the packages’ clinical impact were assessed by comparing (1) agreement between diagnoses based on software output; (2) diagnostic accuracy, sensitivity, and specificity; and (3) diagnostic confidence. Quantitative outputs were also compared to provide context to any diagnostic differences.ResultsDiagnostic agreement between packages was moderate, for distinguishing normal and abnormal volumetry (K = .41–.43) and for specific diagnoses (K = .36–.38). However, each package yielded high inter-observer agreement when distinguishing normal and abnormal profiles (K = .73–.82). Accuracy, sensitivity, and specificity were not different between packages. Diagnostic confidence was different between packages for one rater. Whole brain intracranial volume output differed between software packages (10.73%, p < .001), and normative regional data interpreted for diagnosis correlated weakly to moderately (rs = .12–.80).ConclusionDifferent artificial intelligence software packages for quantitative normative assessment of brain MRI can produce distinct effects at the level of clinical interpretation. Clinics should not assume that different packages are interchangeable, thus recommending internal evaluation of packages before adoption.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00234-022-02898-w.

Abnormal Static and Dynamic Functional Network Connectivity in Patients With Presbycusis.

Aim: This study aimed to investigate abnormal static and dynamic functional network connectivity (FNC) and its association with cognitive function in patients with presbycusis.Methods: In total, 60 patients with presbycusis and 60 age-, sex-, and education-matched healthy controls (HCs) underwent resting-state functional MRI (rs-fMRI) and cognitive assessments. Group independent component analysis (ICA) was carried out on the rs-fMRI data, and eight resting-state networks (RSNs) were identified. Static and dynamic FNCs (sFNC and dFNC) were then constructed to evaluate differences in RSN connectivity between the patients with presbycusis and the HCs. Furthermore, the correlations between these differences and cognitive scores were analyzed.Results: Patients with presbycusis had differences in sFNC compared with HCs, mainly reflected in decreased sFNC in the default mode network (DMN)-left frontoparietal network (LFPN) and attention network (AN)-cerebellum network (CN) pairs, but they had increased sFNC in the auditory network (AUN) between DMN domains. The decreased sFNC in the DMN-LFPN pair was negatively correlated with their TMT-B score (r = –0.441, p = 0.002). Patients with presbycusis exhibited aberrant dFNCs in State 2 and decreased dFNCs between the CN and AN and the visual network (VN). Moreover, the presbycusis group had a shorter mean dwell time (MDT) and fraction time (FT) in State 3 (p = 0.0027; p = 0.0031, respectively).Conclusion: This study highlighted differences in static and dynamic functional connectivity in patients with presbycusis and suggested that FNC may serve as an important biomarker of cognitive performance since abnormal alterations can better track cognitive impairment in presbycusis.

Selective Impairment of Long-Range Default Mode Network Functional Connectivity as a Biomarker for Preclinical Alzheimer's Disease in People with Down Syndrome.

Down syndrome (DS) is associated with increased risk for Alzheimer's disease (AD). In neurotypical individuals, clinical AD is preceded by reduced resting state functional connectivity in the default mode network (DMN), but it is unknown whether changes in DMN connectivity predict clinical onset of AD in DS. Does lower DMN functional connectivity predict clinical onset of AD and cognitive decline in people with DS? Resting state functional MRI (rsfMRI), longitudinal neuropsychological, and clinical assessment data were collected on 15 nondemented people with DS (mean age = 51.66 years, SD = 5.34 years, range = 42-59 years) over four years, during which 4 transitioned to dementia. Amyloid-β (Aβ) PET data were acquired on 13 of the 15 participants. Resting state fMRI, neuropsychological, and clinical assessment data were also acquired on an independent, slightly younger unimpaired sample of 14 nondemented people with DS (mean age = 44.63 years, SD = 7.99 years, range = 38-61 years). Lower functional connectivity between long-range but not short-range DMN regions predicts AD diagnosis and cognitive decline in people with DS. Aβ accumulation in the inferior parietal cortex is associated with lower regional DMN functional connectivity. Reduction of long-range DMN connectivity is a potential biomarker for AD in people with DS that precedes and predicts clinical conversion.

Quantitative susceptibility mapping reveals alterations of dentate nuclei in common types of degenerative cerebellar ataxias.

The cerebellar nuclei are a brain region with high iron content. Surprisingly, little is known about iron content in the cerebellar nuclei and its possible contribution to pathology in cerebellar ataxias, with the only exception of Friedreich’s ataxia. In the present exploratory cross-sectional study, quantitative susceptibility mapping was used to investigate volume, iron concentration and total iron content of the dentate nuclei in common types of hereditary and non-hereditary degenerative ataxias. Seventy-nine patients with spinocerebellar ataxias of types 1, 2, 3 and 6; 15 patients with Friedreich’s ataxia; 18 patients with multiple system atrophy, cerebellar type and 111 healthy controls were also included. All underwent 3 T MRI and clinical assessments. For each specific ataxia subtype, voxel-based and volumes-of-interest-based group analyses were performed in comparison with a corresponding age- and sex-matched control group, both for volume, magnetic susceptiblity (indicating iron concentration) and susceptibility mass (indicating total iron content) of the dentate nuclei. Spinocerebellar ataxia of type 1 and multiple system atrophy, cerebellar type patients showed higher susceptibilities in large parts of the dentate nucleus but unaltered susceptibility masses compared with controls. Friedreich’s ataxia patients and, only on a trend level, spinocerebellar ataxia of type 2 patients showed higher susceptibilities in more circumscribed parts of the dentate. In contrast, spinocerebellar ataxia of type 6 patients revealed lower susceptibilities and susceptibility masses compared with controls throughout the dentate nucleus. Spinocerebellar ataxia of type 3 patients showed no significant changes in susceptibility and susceptibility mass. Lower volume of the dentate nuclei was found to varying degrees in all ataxia types. It was most pronounced in spinocerebellar ataxia of type 6 patients and least prominent in spinocerebellar ataxia of type 3 patients. The findings show that alterations in susceptibility revealed by quantitative susceptibility mapping are common in the dentate nuclei in different types of cerebellar ataxias. The most striking changes in susceptibility were found in spinocerebellar ataxia of type 1, multiple system atrophy, cerebellar type and spinocerebellar ataxia of type 6. Because iron content is known to be high in glial cells but not in neurons of the cerebellar nuclei, the higher susceptibility in spinocerebellar ataxia of type 1 and multiple system atrophy, cerebellar type may be explained by a reduction of neurons (increase in iron concentration) and/or an increase in iron-rich glial cells, e.g. microgliosis. Hypomyelination also leads to higher susceptibility and could also contribute. The lower susceptibility in SCA6 suggests a loss of iron-rich glial cells. Quantitative susceptibility maps warrant future studies of iron content and iron-rich cells in ataxias to gain a more comprehensive understanding of the pathogenesis of these diseases.

No difference in radiologic outcomes for natalizumab patients treated with extended interval dosing compared with standard interval dosing: Real-world evidence from MS PATHS

Extended interval dosing (EID; average dosing interval approximately every 6 weeks) of natalizumab is associated with significantly lower risk of progressive multifocal leukoencephalopathy than standard interval dosing (SID; every 4 weeks) in patients with relapsing-remitting multiple sclerosis (MS). Real-world studies, though limited, suggest that natalizumab effectiveness is generally maintained in patients who switch to EID after initiation of stable treatment with SID. MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions) is a collaborative, multicenter learning health system that generates real-world clinical and MRI data using highly standardized acquisition protocols. We compared MRI outcomes in MS PATHS patients treated with natalizumab EID versus SID. We also compared MRI outcomes in patients treated with natalizumab (EID and/or SID) versus injectable MS platform therapy. Natalizumab infusion data from the TOUCH Prescribing Program database and MS PATHS MRI assessment data from seven US sites as of July 23, 2020, were used to identify patients with relapsing-remitting MS who had received natalizumab EID or SID in the interval between two MRI scans (an MRI segment). Patients who received injectable platform MS therapy between two MRI scans were also identified. MRI data were used to determine the incidence rate and odds of developing new or enlarging T2 lesions, annualized percentage change in T2 lesion volume (T2LV), and annualized percentage change in brain parenchymal fraction (BPF). MRI outcomes were compared for 1) natalizumab EID treatment versus natalizumab SID treatment, 2) natalizumab treatment (EID+SID) versus platform therapy, and 3) natalizumab EID versus platform therapy. Propensity score-based weighting or matching were used to balance covariates at the start of MRI segments for all comparisons. The MRI outcomes observed with natalizumab EID treatment did not differ significantly from those observed with natalizumab SID treatment. The odds ratio for any new or enlarging T2 lesion was 1.07 (95% confidence interval [CI]: 0.93, 1.24; p=0.355), and the rate ratio (95% CI) for new or enlarging T2 lesions was 1.62 (0.93, 2.82; p=0.090). Differences (95% CI) between EID and SID patients in mean annualized percentage change in T2LV and BPF were 1.56% (-3.77%, 6.90%; p=0.566) and -0.11% (-0.25%, -0.10%; p=0.096), respectively. Conversely, when MRI outcomes in natalizumab and platform therapy patients were compared, there were significant differences favoring natalizumab in all assessments: the odds of any new or enlarging T2 lesion (odds ratio: 0.69 [95% CI: 0.64, 0.75]; p<0.001), the incidence rate of new or enlarging T2 lesions (rate ratio: 0.47 [95% CI: 0.37, 0.61]; p<0.001), annualized percentage change (decrease) in T2LV (difference: -3.68% [95% CI: -7.06%, -0.30%]; p=0.033), and annualized percentage change (increase) in BPF (difference: 0.22% [95% CI: 0.16%, 0.29%]; p<0.001). Results of the subgroup comparison of natalizumab EID patients with platform therapy patients were similar to those of the overall-natalizumab-group-versus-platform-therapy comparison. The results indicate that natalizumab EID and SID provide comparable real-world effectiveness on quantitative MRI metrics. These data further demonstrate that natalizumab EID can provide superior real-world effectiveness to injectable platform therapy on quantitative MRI metrics.

NON-CHONDRAL MULTI-TISSUE PATHOLOGY AS ASSESSED BY MRI INCREASES RATES OF QUANTITATIVE MRI-DEFINED CARTILAGE THICKNESS LOSS OVER 24 MONTHS: THE APPROACH STUDY

NON-CHONDRAL MULTI-TISSUE PATHOLOGY AS ASSESSED BY MRI INCREASES RATES OF QUANTITATIVE MRI-DEFINED CARTILAGE THICKNESS LOSS OVER 24 MONTHS: THE APPROACH STUDY

A deep learning pipeline for automatized assessment of spinal MRI

BackgroundThis work evaluates the feasibility, development, and validation of a machine learning pipeline that includes all tasks from MRI input to the segmentation and grading of the intervertebral discs in the lumbar spine, offering multiple different radiological gradings of degeneration as quantitative objective output. MethodsThe pipelines’ performance was analysed on 1′000 T2-weighted sagittal MRI. Binary outputs were assessed with the harmonic mean of precision and recall (DSC) and the area under the precision-recall curve (AUC-PR). Multi-class output scores were averaged and complemented by the Top-2 categorical accuracy. The processing success rate was evaluated on 10′053 unlabelled MRI scans of lumbar spines. ResultsThe midsagittal plane selection achieved an DSC of 74,80% ± 2,99% and an AUC-PR score of 81.71% ± 2.72% (96.91% Top-2 categorical accuracy). The segmentation network obtained a DSC of 91.80% ± 0.44%. The Pfirrmann grading of intervertebral discs in the midsagittal plane was classified with a DSC of 64.08% ± 3.29% and an AUC-PR score of 68.25% ± 6.00% (91.65% Top-2 categorical accuracy). Disc herniations achieved a DSC of 61.57% ± 3.39% and an AUC-PR score of 66.86% ± 5.03%. The cranial endplate defects reached a DSC of 49.76% ± 3.45% and 52.36% ± 1.98% AUC-PR (slightly superior predictions of caudal endplate defect). The binary classifications for the caudal Schmorl's nodes obtained a DSC of 91.58% ± 2.25% with an AUC-PR metric of 96.69% ± 1.58% (similar performance for cranial Schmorl's nodes). Spondylolisthesis was classified with a DSC of 89.03% ± 2.42% and an AUC-PR score of 95.98% ± 1.82%. Annular Fissures were predicted with a DSC of 78.09% ± 7.21% and an AUC-PR score of 86.31% ± 7.45%. Intervertebral disc classifications in the parasagittal plane achieved an equivalent performance. The pipeline successfully processed 98.53% of the provided sagittal MRI scans. ConclusionsThe present deep learning framework has the potential to aid the quantitative evaluation of spinal MRI for an array of clinically established grading systems.

Intrinsic functional brain connectivity is resilient to chronic hypoperfusion caused by unilateral carotid artery stenosis

IntroductionChronic cerebral hypoperfusion caused by asymptomatic high-grade stenosis of the internal carotid artery (ICA) has been associated with impaired cognitive function. Only few studies exist on underlying changes of functional connectivity (FC). Methods20 patients with unilateral high-grade ICA stenosis without MRI lesions and 25 aged-match controls underwent resting-state functional MRI (rsfMRI) and neuropsychological assessment. Patients were examined within ten days before and 6–10 weeks after surgical or interventional revascularization of carotid stenosis. We examined mean resting-state FC ipsi- and contralateral to stenosis and network topology using graph-theoretical measures. ResultsAt baseline, intrahemispheric FC was similar for patients and healthy controls. After revascularization mean FC increased moderately without an effect on network topology. Patients performed worse in TMT B and Stroop test, while performance in global screening tests for dementia (Mini Mental Status Examination, DemTect) were comparable. Test results did not improve after revascularization. ConclusionIn our study population, we find no effect of chronic hypoperfusion on FC and global cognitive function, although we observe minor impairments in processing speed and mental flexibility. The subtle increase of FC after revascularization could indicate excessive upregulation after restoration of perfusion. However, it might as well be a coincidental finding due to the limited sample size.

Adapting UK Biobank imaging for use in a routine memory clinic setting: The Oxford Brain Health Clinic

The Oxford Brain Health Clinic (BHC) is a joint clinical-research service that provides memory clinic patients and clinicians access to high-quality assessments not routinely available, including brain MRI aligned with the UK Biobank imaging study (UKB).In this work we present how we 1) adapted the UKB MRI acquisition protocol to be suitable for memory clinic patients, 2) modified the imaging analysis pipeline to extract measures that are in line with radiology reports and 3) explored the alignment of measures from BHC patients to the largest brain MRI study in the world (ultimately 100,000 participants).Adaptations of the UKB acquisition protocol for BHC patients include dividing the scan into core and optional sequences (i.e., additional imaging modalities) to improve patients’ tolerance for the MRI assessment. We adapted the UKB structural MRI analysis pipeline to take into account the characteristics of a memory clinic population (e.g., high amount of white matter hyperintensities and hippocampal atrophy). We then compared the imaging derived phenotypes (IDPs) extracted from the structural scans to visual ratings from radiology reports, non-imaging factors (age, cognition) and to reference distributions derived from UKB data.Of the first 108 BHC attendees (August 2020-November 2021), 92.5 % completed the clinical scans, 88.0 % consented to use of data for research, and 43.5 % completed the additional research sequences, demonstrating that the protocol is well tolerated. The high rates of consent to research makes this a valuable real-world quality research dataset routinely captured in a clinical service. Modified tissue-type segmentation with lesion masking greatly improved grey matter volume estimation. CSF-masking marginally improved hippocampal segmentation. The IDPs were in line with radiology reports and showed significant associations with age and cognitive performance, in line with the literature. Due to the age difference between memory clinic patients of the BHC (age range 65–101 years, average 78.3 years) and UKB participants (44–82 years, average 64 years), additional scans on elderly healthy controls are needed to improve reference distributions. Current and future work aims to integrate automated quantitative measures in the radiology reports and evaluate their clinical utility.

In-depth characterization of neuroradiological findings in a large sample of individuals with autism spectrum disorder and controls

BackgroundAutism spectrum disorder (ASD) is a group of neurodevelopmental conditions associated with quantitative differences in cortical and subcortical brain morphometry. Qualitative assessment of brain morphology provides complementary information on the possible underlying neurobiology. Studies of neuroradiological findings in ASD have rendered mixed results, and await robust replication in a sizable and independent sample. MethodsWe systematically and comprehensively assessed neuroradiological findings in a large cohort of participants with ASD and age-matched controls (total N = 620, 348 ASD and 272 controls), including 70 participants with intellectual disability (47 ASD, 23 controls). We developed a comprehensive scoring system, augmented by standardized biometric measures. ResultsThere was a higher incidence of neuroradiological findings in individuals with ASD (89.4 %) compared to controls (83.8 %, p = .042). Certain findings were also more common in ASD, in particular opercular abnormalities (OR 1.9, 95 % CI 1.3–3.6) and mega cisterna magna (OR 2.4, 95 % CI 1.4–4.0) reached significance when using FDR, whereas increases in macrocephaly (OR 2.0, 95 % CI 1.2–3.2), cranial deformities (OR 2.4, 95 % CI: 1.0–5.8), calvarian / dural thickening (OR 1.5, 95 % CI 1.0–2.3), ventriculomegaly (OR 3.4, 95 % CI 1.3–9.2), and hypoplasia of the corpus callosum (OR 2.7, 95 % CI 1.1–6.3) did not survive this correction. Furthermore, neuroradiological findings were more likely to occur in isolation in controls, whereas they clustered more frequently in ASD. The incidence of neuroradiological findings was higher in individuals with mild intellectual disability (95.7 %), irrespective of ASD diagnosis. ConclusionThere was a subtly higher prevalence of neuroradiological findings in ASD, which did not appear to be specific to the condition. Individual findings or clusters of findings may point towards the neurodevelopmental mechanisms involved in individual cases. As such, clinical MRI assessments may be useful to guide further etiopathological (genetic) investigations, and are potentially valuable to fundamental ASD research.

PREVALCENCE OF MR‐DECTED CARTILAGE DAMAGE IN KNEES WITH KELLGREN-LAWRENCE 2 & 3 OSTEOARTHRITIS AND IMPLICATIONS FOR CLINICAL TRIALS

Many potential disease-modifying osteoarthritis drugs (DMOADs) have been investigated, but to date no DMOADs that slow or stop disease progression have been approved by the Food and Drug Administration (FDA) or the European Medicines Agency (EMA). A potential reason for the lack of demonstrated efficacy may be reliance on radiographs for defining structural inclusion and exclusion criteria for clinical trials, such as use of joint space width and Kellgren-Lawrence (KL) grade as surrogates for cartilage damage. To estimate the distribution of cartilage damage seen on knee MRI in a sample of knees with radiographic KL 2 and 3 OA that would potentially qualify for a DMOAD trial. We selected knees from the Osteoarthritis Initiative (OAI) that met common structural inclusion criteria for DMOAD trial enrollment at OAI baseline: knees with radiographs centrally graded as KL 2 or 3 and medial minimum joint space width (mJSW) ≥ 1.5mm. A musculoskeletal radiologist with 10 years of experience in semi-quantitative MRI assessment scored knee cartilage damage in the medial and lateral tibiofemoral and patellofemoral compartments using WORMS (Whole-Organ Magnetic Resonance Imaging Score). Coronal intermediate weighted (IW) TSE and sagittal fat-suppressed IW TSE sequences on 3T MRI were used. The WORMS cartilage scores, which are based on both the extent and depth of cartilage damage, were collapsed into 4 categories: no cartilage damage (WORMS 0 and 1), focal partial or full-thickness (PT/FT) cartilage damage (WORMS 2 and 2.5), diffuse partial thickness (PT) cartilage damage (WORMS 3 and 4), and diffuse full-thickness (FT) cartilage damage (WORMS 5 and 6). We estimated the prevalence of each category of cartilage damage in KL2 and KL3 knees; 95% confidence intervals (CI) accounted for clustering at the participant-level since some participants contributed two knees to the analysis. We identified 2,372 participants contributing 3,446 knees with radiographic OA (KL 2 and 3) and medial mJSW ≥ 1.5mm. There were 2,318 KL2 knees and 1,128 KL3 knees. We found no cartilage damage in any compartments in 9.8% (95%CI: 8.5, 11.1) of KL2 knees and 2.0% (95%CI: 1.1, 2.9) of KL3 knees. Cartilage damage was absent in the medial tibiofemoral compartment in 52.4% (95%CI: 50.1, 54.6) of KL2 knees, and 14.4% (95%CI: 12.2, 16.6) of KL3 knees, versus 61% (95%CI: 58.8, 63.2) of KL2 knees and 53.6% (95%CI: 50.4, 56.7) of KL3 knees in the lateral compartment. When medial and lateral compartments were combined, cartilage damage was absent in 34.8% (95%CI: 32.7, 36.9) of the KL2 knees, and 4.3% (95%CI: 3.0, 5.5) of the KL3 knees. Diffuse FT cartilage lesions in the medial compartment were found in 6.1% (95%CI: 5.0, 7.1) of KL2 knees and 42.5% (95%CI: 39.4, 45.6) of KL3 knees. MRI screening prior to clinical trial enrollment may identify a substantial percentage of knees with normal cartilage, as well as knees with diffuse FT cartilage lesions that may not be responsive to DMOADs, depending on the mode of action of a given pharmacological compound. AG has received consultancies fees from Pfizer, Novartis, AstraZeneca, Merck Serono, Regeneron and TissueGene and is shareholder of Boston Imaging Core Lab (BICL), LLC a company providing image assessment services. FWR is shareholder of BICL, LLC and has received consultancies fees from Calibr–California Institute of Biomedical Research and Grünenthal, GmbH. DH receives publication royalties from Wolters-Kluwer. CKK has received consultancy fees from Thuasne, Regeneron, Novartis, Kolon Tissue Gene, Taiwan Liposome, Amzell AZ, LG Chem, Express Scripts, and has received grants from Lilly, Pfizer GSK, Cumberland CORRESPONDENCE ADDRESS: mjarraya@mgh.harvard.edu .

The relationship between adolescents' externalizing and internalizing symptoms and brain development over a period of three years

BackgroundAdolescence is a crucial period for both brain maturation and the emergence of mental health disorders. Associations between brain morphology and internalizing/externalizing symptomatology have been identified in clinical or at-risk samples, but age-related developmental differences were rarely considered. The current study investigated the longitudinal relationship between internalizing/externalizing symptoms and brain development in the absence of psychiatric disorders during early and late adolescence. Methods98 healthy adolescents within two cohorts (younger: 9 years, older: 12 years) participated in annual assessments for three years; a clinical assessment measuring their externalizing and internalizing symptoms (SDQ) and an MRI assessment measuring their brain volume and white matter microstructure, including fractional anisotropy (FA), mean diffusivity (MD) and average path length. ResultsLinear mixed effect models and cross-lagged panel models showed that larger subcortical gray matter volume predicted more externalizing symptoms in older adolescents whereas decreases of subcortical gray matter volume predicted more externalizing symptoms for younger adolescents. Additionally, longer average white matter path length predicted more externalizing symptoms for older adolescents, while decreases in cerebral white matter volume were predictive of more externalizing symptoms for younger adolescents. There were no predictive effects for internalizing symptoms, FA or MD. ConclusionsDelays in subcortical brain maturation, in both early and late adolescence, are associated with increases in externalizing behavior which indicates a higher risk for psychopathology and warrants further investigations.

A Study Protocol for Estimating the Association of De Ritis ratio (AST/ALT) with Outcomes in Patients of Acute Ischemic Stroke

Background: One of the clinical endpoints of atherosclerosis is stroke, the most prominent clinical manifestation of cerebrovascular disease. It is a cerebral blood vessel disease that nourishes the brain. A global health concern is stroke. It is the second most prevalent cause of death worldwide and the fourth leading cause of disability. The underlying pathophysiology in most ischemic strokes is atherosclerosis. Few studies have shown that high AST/ALT ratio was independently corelated with the increased danger of complication and death in cerebrovascular event patients. This research aims to assess the correlation of De Ritis ratio in cases of acute ischaemic stroke at admission and their prognosis at 3 months.&#x0D; Methodology: This will be a observational cross sectional study. About 65 patients with signs suggestive of acute ischemic will be examined. A comprehensive laboratory examination will be carried out. For confirmation of the diagnosis, all patients will undergo CT SCAN or MRI assessment. The primary results of stroke severity on admission will be obtained according to the NIHSS scale. The ranking for NIHSS would be dichotomized to less than 5 and more than 5. For all cases diagnosed with acute ischemic stroke, AST/ALT RATIO will be computed. Data will be analysed with relevant statistical tests.&#x0D; Results Expected: We expect a significant correlation between serum de-Ritis ratio and prognosis of acute ischaemic stroke.

Role of cardiac MRI in the prediction of pre-Fontan end-diastolic ventricular pressure.

Growing evidence has emphasised the importance of ventricular performance in functionally single-ventricle patients, particularly concerning diastolic function. Cardiac MRI has been proposed as non-invasive alternative to pre-Fontan cardiac catheterisation in selected patients. To identify clinical and cardiac magnetic resonance predictors of high pre-Fontan end-diastolic ventricular pressure. In a retrospective single-centre study, 38 patients with functionally univentricular heart candidate for Fontan intervention, who underwent pre-Fontan cardiac catheterisation, beside a comprehensive cardiac MRI, echocardiographic, and clinical assessment were included. Medical and surgical history, cardiac magnetic resonance, cardiac catheterisation, echocardiographic, and clinical data were recorded. We investigated the association between non-invasive parameters and cardiac catheterisation pre-Fontan risk factors, in particular with end-diastolic ventricular pressure. Moreover, the impact of conventional invasive pre-Fontan risk factor on post-operative outcome as also assessed. Post-operative complications were associated with higher end-diastolic ventricular pressure and Mayo Clinic indexes (p < 0.01 and p = 0.05, respectively). At receiver operating characteristic curve analysis end-diastolic ventricular pressure ≥ 10.5 mmHg predicted post-operative complications with a sensitivity of 75% and specificity of 88% (AUC: 0.795, 95% CI 0.576;1.000, p < 0.05). At multivariate analysis, both systemic right ventricle (OR: 23.312, 95% CI: 2.704-200.979, p < 0.01) and superior caval vein indexed flow (OR: 0.996, 95% CI: 0.993-0.999, p < 0.05) influenced end-diastolic ventricular pressure ≥ 10.5 mmHg. A reduced superior caval vein flow, evaluated at cardiac magnetic resonance, is associated with higher end-diastolic ventricular pressure a predictor of early adverse outcome in post-Fontan patients.

Phenotyping of multiple sclerosis lesions according to innate immune cell activation using 18 kDa translocator protein-PET.

Chronic active lesions are promotors of neurodegeneration and disease progression in multiple sclerosis. They harbour a dense rim of activated innate immune cells at the lesion edge, which promotes lesion growth and thereby induces damage. Conventional MRI is of limited help in identifying the chronic active lesions, so alternative imaging modalities are needed. Objectives were to develop a PET-based automated analysis method for phenotyping of chronic lesions based on lesion-associated innate immune cell activation and to comprehensively evaluate the prevalence of these lesions in the various clinical subtypes of multiple sclerosis, and their association with disability. In this work, we use 18 kDa translocator protein-PET imaging for phenotyping chronic multiple sclerosis lesions at a large scale. For this, we identified 1510 white matter T1-hypointense lesions from 91 multiple sclerosis patients (67 relapsing–remitting patients and 24 secondary progressive patients). Innate immune cell activation at the lesion rim was measured using PET imaging and the 18 kDa translocator protein-binding radioligand 11C-PK11195. A T1-hypointense lesion was classified as rim-active if the distribution volume ratio of 11C-PK11195-binding was low in the plaque core and considerably higher at the plaque edge. If no significant ligand binding was observed, the lesion was classified as inactive. Plaques that had considerable ligand binding both in the core and at the rim were classified as overall-active. Conventional MRI and disability assessment using the Expanded Disability Status Scale were performed at the time of PET imaging. In the secondary progressive cohort, an average of 19% (median, interquartile range: 11–26) of T1 lesions were rim-active in each individual patient, compared to 10% (interquartile range: 0–20) among relapsing–remitting patients (P = 0.009). Secondary progressive patients had a median of 3 (range: 0–11) rim-active lesions, versus 1 (range: 0–18) among relapsing–remitting patients (P = 0.029). Among those patients who had rim-active lesions (n = 63), the average number of active voxels at the rim was higher among secondary progressive compared to relapsing–remitting patients (median 158 versus 74; P = 0.022). The number of active voxels at the rim correlated significantly with the Expanded Disability Status Scale (R = 0.43, P < 0.001), and the volume of the rim-active lesions similarly correlated with the Expanded Disability Status Scale (R = 0.45, P < 0.001). Our study is the first to report in vivo phenotyping of chronic lesions at large scale, based on 18 kDa translocator protein-PET. Patients with higher disability displayed a higher proportion of rim-active lesions. The in vivo lesion phenotyping methodology offers a new tool for individual assessment of smouldering (rim-active) lesion burden.

Brain Magnetic Susceptibility is Associated With Slower Gait in Community-Dwelling Older Adults

Age-related slowing of gait is exceedingly common and a robust predictor of various adverse health outcomes in older age. Prior neuroimaging studies have documented diverse non-specific structural brain abnormalities which are related to slow gait; however, the extent to which quantitative susceptibility mapping (QSM), which measures regional magnetic susceptibility in the brain, associates with gait speed remains unexplored. In the current study, 415 non-demented community-dwelling older adults (91 males; 81+/- 7 years) underwent an MRI (Siemens 3T TIM Trio) and in-home motor assessment. Gait speed was measured and averaged across 2 timed 8-ft walks. MR-acquired QSM data were pre-processed, registered to ICBM template, and spatially smoothed with a 5mm FWHM Gaussian kernel. When these maps entered group-level GLMs, voxel-wise associations with gait speed were of interest, after adjusting for demographics. We observed very strong negative associations between gait speed and magnetic susceptibility, such that those with slower gait had higher susceptibility in bilateral inferior frontal, superior temporal, and angular gyri (corrected p<.0005). Robust associations were also observed in the middle frontal, precentral, and postcentral gyri of the right hemisphere. These novel findings suggest that reduced myelination or increased iron accumulation in these brain regions may contribute to impaired gait. Future work will need to determine to what extent these cross-sectional QSM metrics are independent predictors of incident adverse health outcomes when controlling for other common brain imaging abnormalities observed in older adults.