Magnetic Resonance Imaging Markers Research Articles

Subclinical Magnetic Resonance Imaging Markers of Cerebral Small Vessel Disease in Relation to Office and Ambulatory Blood Pressure Measurements.

BackgroundTwenty-four-hour and nighttime blood pressure (BP) levels are more strongly associated with cardiovascular risk than office or daytime BP measurements. However, it remains undocumented which of the office and ambulatory BP measurements have the strongest association and predictive information in relation to the presence of type I, or arteriolosclerosis type, cerebral small vessel diseases (CSVD).MethodsA subset of 429 participants from the Maracaibo Aging Study [aged ≥40 years (women, 73.7%; mean age, 59.3 years)] underwent baseline brain magnetic resonance imaging (MRI) to visualize CSVD, which included log-transformed white matter hyperintensities (log-WMH) volume and the presence (yes/no) of lacunes, cerebral microbleeds (CMB), or enlarged perivascular spaces (EPVS). Linear and logistic regression models were applied to examine the association between CSVD and each +10-mmHg increment in the office and ambulatory systolic BP measurements. Improvement in the fit of nested logistic models was assessed by the log-likelihood ratio and the generalized R2 statistic.ResultsOffice and ambulatory systolic BP measurements were related to log-WMH (β-correlation coefficients ≥0.08; P < 0.001). Lacunes and CMB were only associated with ambulatory systolic BP measurements (odds ratios [OR] ranged from 1.31 [95% confidence interval, 1.10-1.55] to 1.46 [1.17–1.84], P ≤ 0.003). Accounted for daytime systolic BP, both the 24-h (β-correlation, 0.170) and nighttime (β-correlation, 0.038) systolic BP measurements remained related to log-WMH. When accounted for 24-h or daytime systolic BP levels, the nighttime systolic BP retained the significant association with lacunes (ORs, 1.05–1.06; 95% CIs, ≥1.01 to ≤ 1.13), whereas the 24-h and daytime systolic BP levels were not associated with lacunes after adjustments for nighttime systolic BP (ORs, ≤ 0.88; 95% CI, ≥0.77 to ≤ 1.14). On top of covariables and office systolic BP, ambulatory systolic BP measurements significantly improved model performance (1.05% ≥ R2 ≤ 3.82%). Compared to 24-h and daytime systolic BP, nighttime systolic BP had the strongest improvement in the model performance; for WMH (1.46 vs. 1.05%) and lacunes (3.06 vs. ≤ 2.05%).ConclusionsTwenty-four-hour and nighttime systolic BP were the more robust BP measurements associated with CSVD, but the nighttime systolic BP level had the strongest association. Controlling ambulatory BP levels might provide additional improvement in the prevention of CSVD.

MRI Markers of Small Vessel Disease and the APOE Allele in Cognitive Impairment.

ObjectiveThe apolipoprotein E (APOE) ε4 allele is the main genetic risk factor for dementia and Alzheimer's disease (AD), but the underlying mechanism for the increased risk is not well understood. Cerebral small vessel disease (SVD) is prevalent among patients with cognitive impairment and is thought to play an important role in the pathophysiology of dementia. We aimed to investigate the association between the APOE ε genotype and magnetic resonance imaging (MRI) markers of SVD in a memory clinic population.Material and MethodsThis is a cross-sectional study with a total of 520 patients undergoing dementia investigation, including an MRI brain scan and APOE genotyping in all patients enrolled, and cerebrospinal fluid (CSF) analysis for routine AD biomarkers in 399 patients. MR images were assessed for markers of SVD: cerebral microbleeds (CMBs), cortical superficial siderosis, intracerebral hemorrhage, white matter hyperintensities, lacunar infarcts, and enlarged perivascular spaces.ResultsApolipoprotein E carriers with AD had a higher number of CMBs when looking at all brain regions and lobar brain regions (p < 0.001). A lower number of CMBs were seen in APOE ε2 (p < 0.05), ε3 and ε3/3 carriers (p < 0.001) when looking at all brain regions. A higher number of CMBs in deep and infratentorial regions were seen in APOE ε2 and ε3 (p < 0.05). In APOE ε4/4 carriers, CMBs, cortical superficial siderosis, white matter hyperintensities, and enlarged perivascular spaces were associated with lower levels of CSF amyloid β (Aβ) 42 in the whole cohort, and in individuals with AD and mild cognitive impairment (p < 0.05).ConclusionApolipoprotein E ε4 is associated with MRI markers of SVD related to amyloid pathology, specifically CMBs and Aβ42 plaque formation in the brain, as reflected by decreased CSF Aβ42 levels, whereas APOE ε3 and ε2 are associated with the markers of hypertensive arteriopathy, as reflected by the association with CMBs in deep and infratentorial brain regions.

Percreta score to differentiate between placenta accreta and placenta percreta with ultrasound and MR imaging.

The objective of this study was to assess the performance of ultrasound and magnetic resonance imaging (MRI) features in helping to classify the type of placenta accreta spectrum (PAS; accreta/increta vs percreta), alone or combined in a predictive score. We conducted a retrospective study in 82 pregnant women with PAS who underwent ultrasound and MRI examination of the pelvis before delivery (from an initial cohort of 185 women with PAS). We estimated the sensitivity, specificity and accuracy of MRI and ultrasound in the diagnosis of the type of PAS. We analyzed cesarean and imaging features using univariable logistic regression analysis. We constructed a nomogram to predict the risk of placenta percreta and validated it with bootstrap resampling, then used receiver operating characteristic curves to assess the performance of the model in distinguishing between placenta percreta and placenta accreta/increta. Among the 82 patients, 29 (35%) had placenta accreta/increta and 53 (65%) had placenta percreta. The best features to discriminate between placenta accreta/increta and placenta percreta with ultrasound were increased vascularization at the uterine serosa-bladder wall interface (odds ratio [OR]7.93; 95% confidence interval [CI] 2.78-24.99; p < 0.01) and the number of lacunae without a hyperechogenic halo (OR 1.36; 95% CI 1.14-1.67; p= 0.012). Concerning MRI markers, heterogeneous placenta (OR 12.89; 95% CI 3.05-89.16; p=0.002), dark intraplacental bands (OR 12.89; 95% CI 3.05-89.16; p=0.002) and bladder wall interruption (OR 15.89; 95% CI 4.78-73.33; p < 0.001) had a higher OR in discriminating placenta accreta/increta from placenta percreta. The nomogram yielded areas under the curve of 0.841 (95% CI 0.754-0.927) and 0.856 (95% CI 0.767-0.945), after bootstrap resampling, for the accurate prediction of placenta percreta. The nomogram we developed to predict the risk of placenta percreta among patients with PAS had good discriminative capabilities. This performance and its impact on maternal morbidity should be confirmed by future prospective studies.

FLAIR Vascular Hyperintensity: An Important MRI Marker in Patients with Transient Ischemic Attack.

PurposeWe aimed to investigate the prevalence of fluid-attenuated inversion recovery (FLAIR) vascular hyperintensities (FVHs) and the clinical–radiological correlation in transient ischemic attack (TIA) patients.Materials and MethodsWe performed a retrospective analysis of TIA patients who had undergone magnetic resonance imaging (MRI) within 24 h of symptom onset. Two independent neuroradiologists investigated the presence of FVHs, large-artery severe stenosis or occlusion (LASO) in magnetic resonance angiograms, and the nature of factors associated with FVH.ResultsA total of 207 patients were enrolled in this study. FVHs were detected in 42 (20.3%) patients, in whom atrial fibrillation (AF) was confirmed in 25 (59.5%) cases and LASO was confirmed in 30 (71.4%) cases. The corresponding figures were 33 (20.0%) and 10 (6.1%), respectively, for the 165 FVH-negative patients. Logistic regression analysis showed that time from symptom onset to MRI (odds ratio [OR] = 0.82, 95% CI 0.76–0.97, p = 0.042), previous stroke (OR = 2.95, 95% CI 1.58–6.74, p = 0.002), AF (OR = 5.83, 95% CI 2.24–9.46, p < 0.001), and LASO (OR = 4.28, 95% CI 2.96–10.28, p < 0.001) were independently associated with FVH. Overall, the sensitivity and specificity of FVH for predicting LASO were 0.75 and 0.93, respectively, and the positive predictive value, negative predictive value, and accuracy were 0.71, 0.94, and 0.89, respectively. The area under the receiver operating characteristic curve was 0.839. FVH-positive TIA patients with LASO had less AF (14 [46.7%] versus 11 [91.7%], p = 0.019) and longer times from symptom onset to MRI (6.8 ± 2.8 h versus 4.8 ± 1.3 h, p = 0.004) than those without LASO.ConclusionThe presence of FVH could be an important marker in TIA patients. Many factors, including LASO, AF, and time from symptom onset to MRI, are associated with the detection of FVH.

Implication of Cerebral Small-Vessel Disease on Perihematomal Edema Progress in Patients With Hypertensive Intracerebral Hemorrhage.

Perihematomal edema (PHE) is an important determinant of outcome in spontaneous intracerebral hemorrhage (ICH) due to cerebral small vessel disease (CSVD). However, it is not known to date whether the severity of CSVD is associated with the extent of PHE progression in the acute phase. To investigate the association between the magnetic resonance imaging (MRI) marker of severe chronic-ischemia cerebral small vessel changes (sciSVC) and PHE growth or hematoma absorption among ICH patients with hypertension. Retrospective. Three hundred and sixty-eight consecutive hypertensive ICH patients without surgical treatment. 3 T; spin-echo echo-planar imaging-diffusion-weighted imaging (DWI); T2-weighted, fluid-attenuated inversion recovery (FLAIR), T2*-weighted gradient-recalled echo and T1-weighted. The hematoma and PHE volumes at 24hours and 5 days after symptom onset were measured in 121 patients with spontaneous ICH who had been administered standard medical treatment. Patients were grouped into two categories: those with sciSVC and those without. The imaging marker of sciSVC was defined as white matter hyperintensities (WMHs) Fazekas 2-3 combined cavitating lacunes. Univariable analyses, χ2 test, Mann-Whitney U test, and multiple linear regression. The presence of sciSVC (multiple lacunes and confluent WMH) had a significant negative influence on PHE progress (Beta=-5.3mL, 95% CI=-10.3mL to -0.3mL), and hematoma absorption (Beta=-3.2mL, 95% CI=-5.9mL to -0.4mL) compared to that observed in the absence of sciSVC, as determined by multivariate linear regression analysis. The presence of sciSVC (multiple lacunes and confluent WMH) negatively influenced hematoma absorption and PHE progress in ICH patients. 4 TECHNICAL EFFICACY: Stage 3.

A Role for Data Science in Precision Nutrition and Early Brain Development.

Multimodal brain magnetic resonance imaging (MRI) can provide biomarkers of early influences on neurodevelopment such as nutrition, environmental and genetic factors. As the exposure to early influences can be separated from neurodevelopmental outcomes by many months or years, MRI markers can serve as an important intermediate outcome in multivariate analyses of neurodevelopmental determinants. Key to the success of such work are recent advances in data science as well as the growth of relevant data resources. Multimodal MRI assessment of neurodevelopment can be supplemented with other biomarkers of neurodevelopment such as electroencephalograms, magnetoencephalogram, and non-imaging biomarkers. This review focuses on how maternal nutrition impacts infant brain development, with three purposes: (1) to summarize the current knowledge about how nutrition in stages of pregnancy and breastfeeding impact infant brain development; (2) to discuss multimodal MRI and other measures of early neurodevelopment; and (3) to discuss potential opportunities for data science and artificial intelligence to advance precision nutrition. We hope this review can facilitate the collaborative march toward precision nutrition during pregnancy and the first year of life.

P885: PROSPECTIVE ASSESSMENT OF MYELOMA TUMOUR BURDEN AND BONE DISEASE USING DW-MRI AND EXPLORATORY BONE BIOMARKERS

Background: Key clinical priorities for multiple myeloma (MM) are to reduce tumour burden and complications, of which lytic bone disease is the major cause of morbidity. To guide treatment, there is a pressing need for biomarkers that can accurately quantify MM tumour burden and associated bone disease. To this end, Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) and bone turnover markers are promising radiological and serum metrics, respectively, although their clinical value in prospective assessment is unclear. Aims: LOOMIS was a single-centre observational cohort study that evaluated the relative merits of DW-MRI and bone turnover markers in prospectively assessing tumour burden and bone disease when added to standard clinical assessment, in patients with MM and monoclonal gammopathy of undetermined significance (MGUS). Methods: A total of 67 patients were enrolled (14 newly diagnosed MM, 12 relapsed MM, 15 smouldering MM, 14 MGUS and 12 healthy volunteers) between March 2018 and March 2020. At baseline (and 6-month follow-up for MM/MGUS), participants had a DW-MRI scan and serum measurements of established (P1NP, CTX-1, ALP) and exploratory (DKK1, sclerostin, RANKL:OPG ratio) bone turnover markers. MM/MGUS patients additionally had standard myeloma bloods and Dual-Energy X-ray Absorptiometry (DXA) at each visit, as correlates of tumour burden and bone loss. DW-MRI scans were double reported by expert Radiologists for Apparent Diffusion Coefficient (ADC) measurements of lytic bone lesion(s), and Myeloma Response Assessment and Diagnosis System (MY-RADS) Response Assessment Category (RAC) scoring. Patients were classified by International Myeloma Working Group (IMWG) response criteria as a clinical correlate of therapy response. Results: On assessment of baseline tumour burden, there was no correlation between single lesion DW-MRI ADC and serum paraprotein [p>0.05]; however, there was moderate positive correlation between serum DKK1 and serum paraprotein [r=0.39, p=0.04]. At follow-up, radiological MY-RADS RAC scoring correlated with conventional IMWG response criteria [p=0.015]; additionally, longitudinal relative change in serum DKK1 differed between IMWG-defined therapy responders (37% decrease) and non-responders (15% increase) [p<0.01]. On baseline assessment of bone loss, there was moderate positive correlation between serum sclerostin and DXA bone mineral density at femoral neck [r=0.40, p<0.01] and lumbar spine [r=0.54, p<0.001]. At follow-up, there was a moderate negative correlation between longitudinal % change in the RANKL:OPG ratio and % change in DXA bone mineral density at femoral neck [r= -0.45, p<0.01]. Summary/Conclusion: Our prospective trial validates DW-MRI-based MY-RADS RAC scoring as a qualitative radiological tool to assess therapy response. Whilst previous work has supported single lytic lesion ADC measurements as a correlate of tumour volume, we did not find this; small sample size and prior chemotherapy in our study may have limited our ability to detect this. In comparison, serum bone turnover markers such as DKK1 may provide a more global measure to quantify myeloma burden both at baseline diagnosis and longitudinally with therapy. Additionally, our data highlight serum sclerostin and RANKL:OPG ratio as potential biomarkers to assess and monitor bone loss. Overall, our study highlights emerging radiological and serum biomarkers of tumour burden and associated bone loss in MM and MGUS, which merit further exploration alongside uniformly treated cohorts, to better understand their clinical utility.

Enlarged Perivascular Spaces in the Basal Ganglia Independently Related to Gait Disturbances in Older People With Cerebral Small Vessel Diseases.

Background and ObjectiveGait disturbances are common in older people and are associated with adverse consequences, e.g., falls and institutionalization. Enlarged perivascular spaces in the basal ganglia (BG-EPVS) are considered an magnetic resonance imaging (MRI) marker of cerebral small vessel diseases (CSVD). However, the consequences of BG-EPVS are largely unknown. Previous studies showed that other CSVD markers were related to gait disturbances. However, the relation between BG-EPVS and gait performance is unclear. Therefore, we aimed to explore the relation between BG-EPVS and gait performance in elderly individuals.MethodsWe recruited older people with CSVD in the Neurology Department of our hospital from December 1, 2020 to October 31, 2021. Participants with BG-EPVS > 20 on the unilateral side of the basal ganglia slice containing the maximum number were classified into the BG-EPVS group (n = 78), and the rest were classified into the control group (n = 164). Quantitative gait parameters and gait variability were provided by the Intelligent Device for Energy Expenditure and Activity (IDEEA; MiniSun, United States) gait analysis system. Semiquantitative gait assessment was measured with the Tinetti test. Point-biserial correlation and multivariate linear regression analysis were performed to investigate the association between BG-EPVS and gait performance.ResultsThe BG-EPVS group had a slower gait speed and cadence, shorter stride length, longer stance phase percentage, smaller pre-swing angle and footfall, and lower Tinetti gait test and balance test scores compared with those in the control group (P < 0.05). There were no statistical differences in stride length variability and stride time variability between the two groups (P > 0.05). A correlation analysis showed that BG-EPVS were negatively related to gait speed, cadence, stride length, pre-swing angle, and footfall (γrange = −0.497 to −0.237, P < 0.001) and positively related to stance phase percentage (γ = 0.269, P < 0.001). BG-EPVS was negatively related to the score of the Tinetti gait test (γ = −0.449, P < 0.001) and the balance test (γ = −0.489, P < 0.001). The multiple linear regression analysis indicated that BG-EPVS was an independent risk factor for gait disturbances and poor balance after adjusting for confounders, including other CSVD markers.ConclusionLarge numbers of BG-EPVS were independently related to gait disturbances in older people with CSVD. This finding provides information about the consequences of BG-EPVS and risk factors for gait disturbances.

Relationship Between Arterial Stiffness Index, Pulse Pressure, and Magnetic Resonance Imaging Markers of White Matter Integrity: A UK Biobank Study.

BackgroundAlzheimer’s disease and dementia in general constitute one of the major public health problems of the 21st century. Research in arterial stiffness and pulse pressure (PP) play an important role in the quest to reduce the risk of developing dementia through controlling modifiable risk factors.ObjectiveThe aim of the study is to investigate the association between peripheral PP, arterial stiffness index (ASI) and brain integrity, and to discover if ASI is a better predictor of white matter integrity than peripheral PP.Materials and Methods17,984 participants 63.09 ± 7.31 from the UK Biobank were used for this study. ASI was estimated using infrared light (photoplethysmography) and peripheral PP was calculated by subtracting the diastolic from the systolic brachial blood pressure value. Measure of fractional anisotropy (FA) was obtained from diffusion imaging to estimate white matter microstructural integrity. White matter hyperintensities were segmented from the combined T1 and T2-weighted FLAIR images as a measure of irreversible white matter damage.ResultsAn important finding is that peripheral PP better predicts white matter integrity when compared to ASI. This finding is consistent until 75 years old. Interestingly, no significant relationship is found between either peripheral PP or ASI and white matter integrity after 75 years old.ConclusionThese results suggest that ASI from plethysmography should not be used to estimate cerebrovascular integrity in older adults and further question the relationship between arterial stiffness, blood pressure, and white matter damage after the age of 75 years old.

Imaging Characteristics for Predicting Cognitive Impairment in Patients With Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy.

ObjectivesPatients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) show various clinical symptoms, including migraine, recurrent stroke, and cognitive impairment. We investigated the associations between magnetic resonance imaging (MRI) markers of small vessel disease and neuropsychological tests and identified the MRI characteristics for predicting cognitive impairment in patients with CADASIL.MethodsSubjects included 60 CADASIL patients diagnosed with genetic tests and registered in the Japanese CADASIL REDCap database between June 2016 and December 2020. Patient information including clinical data, modified Rankin Scale (mRS); MRI findings of small vessel disease including periventricular and deep white matter lesions (WML), lacunar infarcts, and cerebral microbleeds (CMBs); and neuropsychological tests, including the Japanese version of the Mini-Mental State Examination (MMSE), the Japanese version of the Montreal Cognitive Assessment (MoCA-J), and the Frontal Assessment Battery (FAB), were evaluated.ResultsData from 44 CADASIL patients were eligible for this study, compared between patients with and without dementia. Regarding the neuroimaging findings, the Fazekas score of periventricular and deep WML was higher in patients with dementia (periventricular, p = 0.003; deep, p = 0.009). The number of lacunar infarcts was higher in patients with dementia (p = 0.001). The standardized partial regression coefficient (SPRC) in MoCA-J was 0.826 (95% CI, 0.723–0.942; p = 0.005) for the number of CMBs. The SPRC in MMSE was 0.826 (95% CI, 0.719–0.949; p = 0.007) for the number of CMBs. The SPRC for FAB decreased significantly to 0.728 (95% CI, 0.551–0.960; p = 0.024) for the number of lacunar infarcts. Receiver operating characteristic (ROC) curves for dementia showed that in the number of lacunar infarcts, a cut-off score of 5.5 showed 90.9% sensitivity and 61.1% specificity. For the number of CMBs, a cut-off score of 18.5 showed 45.5% sensitivity and 100% specificity.ConclusionThe characteristic MRI findings were that CADASIL patients with dementia had severe WML, both periventricular and deep, and a larger number of lacunar infarcts than those without dementia. The risk of dementia may be associated with ≥ 6 lacunar infarcts, ≥19 CMBs, or a Fazekas scale score of 3 in periventricular and deep WML.

Serum neurofilament light chain concentration predicts disease worsening in multiple sclerosis

Background: Serum neurofilament light (sNfL) chain is a promising biomarker reflecting neuro-axonal injury in multiple sclerosis (MS). However, the ability of sNfL to predict outcomes in real-world MS cohorts requires further validation. Objective: The aim of the study is to investigate the associations of sNfL concentration, magnetic resonance imaging (MRI) and retinal optical coherence tomography (OCT) markers with disease worsening in a longitudinal European multicentre MS cohort. Methods: MS patients (n = 309) were prospectively enrolled at four centres and re-examined after 2 years (n = 226). NfL concentration was measured by single molecule array assay in serum. The patients’ phenotypes were thoroughly characterized with clinical examination, retinal OCT and MRI brain scans. The primary outcome was disease worsening at median 2-year follow-up. Results: Patients with high sNfL concentrations (⩾8 pg/mL) at baseline had increased risk of disease worsening at median 2-year follow-up (odds ratio (95% confidence interval) = 2.8 (1.5–5.3), p = 0.001). We found no significant associations of MRI or OCT measures at baseline with risk of disease worsening. Conclusion: Serum NfL concentration was the only factor associated with disease worsening, indicating that sNfL is a useful biomarker in MS that might be relevant in a clinical setting.

Correction to: Longitudinal Progression of Magnetic Resonance Imaging Markers and Cognition in Dutch-Type Hereditary Cerebral Amyloid Angiopathy.

Correction to: Longitudinal Progression of Magnetic Resonance Imaging Markers and Cognition in Dutch-Type Hereditary Cerebral Amyloid Angiopathy.

Mapping microglia and astrocyte activation in vivo using diffusion MRI.

While glia are increasingly implicated in the pathophysiology of psychiatric and neurodegenerative disorders, available methods for imaging these cells in vivo involve either invasive procedures or positron emission tomography radiotracers, which afford low resolution and specificity. Here, we present a noninvasive diffusion-weighted magnetic resonance imaging (MRI) method to image changes in glia morphology. Using rat models of neuroinflammation, degeneration, and demyelination, we demonstrate that diffusion-weighted MRI carries a fingerprint of microglia and astrocyte activation and that specific signatures from each population can be quantified noninvasively. The method is sensitive to changes in glia morphology and proliferation, providing a quantitative account of neuroinflammation, regardless of the existence of a concomitant neuronal loss or demyelinating injury. We prove the translational value of the approach showing significant associations between MRI and histological microglia markers in humans. This framework holds the potential to transform basic and clinical research by clarifying the role of inflammation in health and disease.

Presence of Magnetic Resonance Imaging-Defined Inflammation Particularly in Overweight and Obese Women Increases Risk of Radiographic Knee Osteoarthritis: The POMA Study.

The present study was undertaken to assess whether the odds for incident radiographic osteoarthritis (OA) differ between men and women in regard to body mass index (BMI) and inflammatory magnetic resonance imaging (MRI) markers 1 and 2 years prior, and whether the presence of inflammation on MRI differs between normal-weight and overweight/obese individuals who develop radiographic OA up to 4 years prior. We studied 355 knees from the Osteoarthritis Initiative study that developed incident radiographic OA and 355 matched controls. MRIs were read for effusion-synovitis and Hoffa-synovitis for up to 4 consecutive annual time points. Subjects were classified as normal-weight (BMI <25), overweight (BMI ≥25 and <30), or obese (BMI ≥30). Conditional logistic regression was used to assess odds of incident radiographic OA for effusion-synovitis and Hoffa-synovitis at 1 and 2 years prior to radiographic OA incidence (i.e., "P-1" and "P-2") considering BMI category. Bivariate logistic regression was used to assess odds of inflammation for cases only. One hundred seventy-eight (25.1%) participants were normal weight, 283 (39.9%) overweight, and 249 (35.1%) obese. At P-2, being overweight with Hoffa-synovitis, which had an odds ratio [OR] of 3.26 (95% confidence interval [95% CI] 1.39-7.65), or effusion-synovitis (OR 3.56 [95% CI 1.45-8.75]) was associated with greater odds of incident radiographic OA in women. For those with incident radiographic OA, there were no increased odds of synovitis in the overweight/obese subgroup for most time points, but increased odds for effusion-synovitis were observed at P-2 (OR 2.21 [95% CI 1.11-4.43]). Presence of inflammatory markers seems to play a role especially in overweight women, while obese women have increased odds for radiographic OA also in the absence of these markers.

Cognitive Functions Associated with Brain Imaging Markers in Patients with Psoriasis.

Psoriasis is a severe inflammatory disease associated with a higher comorbidity of depression, cognitive dysfunction and brain atrophy. The association between psoriasis, magnetic resonance imaging (MRI) markers and cognitive impairment has rarely been investigated, and the existing results are conflicting. Methods. This study included 89 subjects (53 patients with psoriasis and 36 healthy controls). The severity of psoriasis was evaluated using the Psoriasis Area and Severity Index (PASI) score; for depression, the Hospital Anxiety and Depression Scale (HADS) scale was used. Neuropsychological tests were also applied, including a Trail Making Test (TMT) as well as Digit Span, Stroop, Verbal Fluency and Rey Auditory Verbal Learning tests. MRI scans were performed using a 1.5 T scanner. Brain volumetry, white matter lesions, grey matter and white matter were evaluated. The extent of these changes was assessed on the Fazekas scale. The differences between groups were evaluated using a Student’s t-test and a Mann-Whitney U test, and a Pearson correlation analysis was also performed. Results. Patients with psoriasis presented worse achievements on all the neuropsychological tests and showed more intense changes on MRI compared to healthy controls. The severity of psoriasis as determined by PASI scores was associated with depression, and a greater psychomotor slowness severity of changes in the brain was associated with poorer results on the neurological tests. Conclusions. Our results indicate the possibility of progressive brain atrophy related to cognitive decline in psoriasis.

Higher Dietary Inflammatory Index scores are associated with brain MRI markers of brain aging: Results from the Framingham Heart Study Offspring cohort.

We investigated cross-sectional associations between the Dietary Inflammatory Index (DII) and measures of brain volume and cerebral small vessel disease among participants of the Framingham Heart Study Offspring cohort. A total of 1897 participants (mean ± standard deviation, age 62±9) completed Food Frequency Questionnaires and brain magnetic resonance imaging (MRI). Higher (pro-inflammatory) DII scores, averaged across a maximum of three time points, were associated with smaller total brain volume (beta ± standard error: -0.16 ± 0.03; P < .0001) after adjustment for demographic, clinical, and lifestyle covariates. In addition, higher DII scores were associated with smaller total gray matter volume (-0.08 ± 0.03; P = .003) and larger lateral ventricular volume (0.04 ± 0.02; P = .03). No associations were observed with other brain MRI measures. Our findings showed associations between higher DII scores and global brain MRI measures. As we are one of the first groups to report on the associations between higher DII scores and brain volume, replication is needed to confirm our findings.

Determinants and Temporal Dynamics of Cerebral Small Vessel Disease: 14-Year Follow-Up

Background:The aim of this study is to investigate the temporal dynamics of small vessel disease (SVD) and the effect of vascular risk factors and baseline SVD burden on progression of SVD with 4 neuroimaging assessments over 14 years in patients with SVD.Methods:Five hundred three patients with sporadic SVD (50–85 years) from the ongoing prospective cohort study (RUN DMC [Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort]) underwent baseline assessment in 2006 and follow-up in 2011, 2015, and 2020. Vascular risk factors and magnetic resonance imaging markers of SVD were evaluated. Linear mixed-effects model and negative binomial regression model were used to examine the determinants of temporal dynamics of SVD markers.Results:A total of 382 SVD patients (mean [SD] 64.1 [8.4]; 219 men and 163 women) who underwent at least 2 serial brain magnetic resonance imaging scans were included, with mean (SD) follow-up of 11.15 (3.32) years. We found a highly variable temporal course of SVD. Mean (SD) WMH progression rate was 0.6 (0.74) mL/y (range, 0.02–4.73 mL/y) and 13.6% of patients had incident lacunes (1.03%/y) over the 14-year follow-up. About 4% showed net WMH regression over 14 years, whereas 38 out of 361 (10.5%), 5 out of 296 (2%), and 61 out of 231 (26%) patients showed WMH regression for the intervals 2006 to 2011, 2011 to 2015, and 2015 to 2020, respectively. Of these, 29 (76%), 5 (100%), and 57 (93%) showed overall progression across the 14-year follow-up, and the net overall WMH change between first and last scan considering all participants was a net average WMH progression over the 14-year period. Older age was a strong predictor for faster WMH progression and incident lacunes. Patients with mild baseline WMH rarely progressed to severe WMH. In addition, both baseline burden of SVD lesions and vascular risk factors independently and synergistically predicted WMH progression, whereas only baseline SVD burden predicted incident lacunes over the 14-year follow-up.Conclusions:SVD shows pronounced progression over time, but mild WMH rarely progresses to clinically severe WMH. WMH regression is noteworthy during some magnetic resonance imaging intervals, although it could be overall compensated by progression over the long follow-up.

Multivariable Modeling of Biomarker Data From the Phase I Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium.

To determine the optimal combination of imaging and biochemical biomarkers for use in the prediction of knee osteoarthritis (OA) progression. The present study was a nested case-control trial from the Foundation of the National Institutes of Health OA Biomarkers Consortium that assessed study participants with a Kellgren/Lawrence grade of 1-3 who had complete biomarker data available (n = 539 to 550). Cases were participants' knees that had radiographic and pain progression between 24 and 48 months compared to baseline. Radiographic progression only was assessed in secondary analyses. Biomarkers (baseline and 24-month changes) that had a P value of <0.10 in univariate analysis were selected, including quantitative cartilage thickness and volume on magnetic resonance imaging (MRI), semiquantitative MRI markers, bone shape and area, quantitative meniscal volume, radiographic progression (trabecular bone texture [TBT]), and serum and/or urine biochemical markers. Multivariable logistic regression models were built using 3 different stepwise selection methods (complex models versus parsimonious models). Among baseline biomarkers, the number of locations affected by osteophytes (semiquantitative), quantitative central medial femoral and central lateral femoral cartilage thickness, patellar bone shape, and semiquantitative Hoffa-synovitis predicted OA progression in most models (C statistic 0.641-0.671). In most models, 24-month changes in semiquantitative MRI markers (effusion-synovitis, meniscal morphologic changes, and cartilage damage), quantitative central medial femoral cartilage thickness, quantitative medial tibial cartilage volume, quantitative lateral patellofemoral bone area, horizontal TBT (intercept term), and urine N-telopeptide of type I collagen predicted OA progression (C statistic 0.680-0.724). A different combination of imaging and biochemical biomarkers (baseline and 24-month change) predicted radiographic progression only, which had a higher C statistic of 0.716-0.832. The present study highlights the combination of biomarkers with potential prognostic utility in OA disease-modifying trials. Properly qualified, these biomarkers could be used to enrich future trials with participants likely to experience progression of knee OA.

The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy.

ABSTRACTBackgroundThe second consensus criteria for the diagnosis of multiple system atrophy (MSA) are widely recognized as the reference standard for clinical research, but lack sensitivity to diagnose the disease at early stages.ObjectiveTo develop novel Movement Disorder Society (MDS) criteria for MSA diagnosis using an evidence‐based and consensus‐based methodology.MethodsWe identified shortcomings of the second consensus criteria for MSA diagnosis and conducted a systematic literature review to answer predefined questions on clinical presentation and diagnostic tools relevant for MSA diagnosis. The criteria were developed and later optimized using two Delphi rounds within the MSA Criteria Revision Task Force, a survey for MDS membership, and a virtual Consensus Conference.ResultsThe criteria for neuropathologically established MSA remain unchanged. For a clinical MSA diagnosis a new category of clinically established MSA is introduced, aiming for maximum specificity with acceptable sensitivity. A category of clinically probable MSA is defined to enhance sensitivity while maintaining specificity. A research category of possible prodromal MSA is designed to capture patients in the earliest stages when symptoms and signs are present, but do not meet the threshold for clinically established or clinically probable MSA. Brain magnetic resonance imaging markers suggestive of MSA are required for the diagnosis of clinically established MSA. The number of research biomarkers that support all clinical diagnostic categories will likely grow.ConclusionsThis set of MDS MSA diagnostic criteria aims at improving the diagnostic accuracy, particularly in early disease stages. It requires validation in a prospective clinical and a clinicopathological study. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Longitudinal Progression of Magnetic Resonance Imaging Markers and Cognition in Dutch-Type Hereditary Cerebral Amyloid Angiopathy.

Background:Hemorrhagic and ischemic magnetic resonance imaging lesions as well as the more recently described decrease in vasomotor reactivity have been suggested as possible biomarkers for cerebral amyloid angiopathy (CAA). Analyses of these markers have been primarily cross-sectional during the symptomatic phase of the disease, with little data on their longitudinal progression, particularly in the presymptomatic phase of the disease when it may be most responsive to treatment. We used the unique opportunity provided by studying Dutch-type hereditary cerebral amyloid angiopathy (D-CAA) to determine longitudinal progression of CAA biomarkers during the presymptomatic as well as the symptomatic phase of the disease.Methods:In this longitudinal case-control study, magnetic resonance imaging markers and cognitive performance were assessed at baseline and after ≈4 years in 10 presymptomatic and 6 symptomatic D-CAA mutation carriers and 20 control subjects. These magnetic resonance imaging markers included hemorrhagic and ischemic manifestations, measurements of cerebral blood flow, and vasomotor reactivity to visual stimulation.Results:In presymptomatic D-CAA mutations carriers, vasomotor reactivity showed a decline over time for blood-oxygen-level–dependent amplitude (P=0.011) and prolongation of time to peak (P<0.001). In contrast, no significant changes in hemorrhagic markers, ischemic markers, cerebral blood flow, and cognition were found. In symptomatic D-CAA mutation carriers, the number of intracerebral hemorrhages increased over the 4-year period (P=0.007).Conclusions:Our findings indicate that in the presymptomatic phase of D-CAA, cerebrovascular reactivity measured by the blood-oxygen-level–dependent amplitude and time to peak to visual stimulation progressively worsens and can thus be regarded as a disease progression marker. In the symptomatic phase, the most salient marker of progression appears to be recurrent intracerebral hemorrhage.