Total Lesion Volume Research Articles

Diagnostic utility of the MTA-Score depending on age and cerebral microangiopathy in times of automated volumetry

To investigate the diagnostic value of the MTA score according to age, cerebral small vessel disease and in times of automated volumetry. Retrospective analysis of patients with subjective cognitive decline (SCD), amnestic mild cognitive impairment (aMCI), Alzheimer's disease (AD) and mixed dementia (MD) who presented to our outpatient dementia clinic between February 2018 and October 2020. Patients underwent cranial magnetic resonance imaging (MRI) including specific MRI sequences needed for automated volumetry. MRI data sets were analyzed regarding MTA score, Fazekas score, hippocampal und temporal lobe percentile and total white matter lesion volume. Within the study period, 242 patients (100 male, 142 female, mean age 74.7±9.9 years) with SCD (n=20), aMCI (n=110), AD (n=62) and MD (n=50) were analyzed. MTA score strongly correlated with age (ρ=0.545; p<0.001), especially regarding the aMCI and AD group. MTA score differentiated only between prodromal and dementia stages (aMCI vs. AD: p=0.005), whereas hippocampal percentile also showed a trend in differentiating between SCD and aMCI. There was a correlation between MTA score and hippocampal percentile (ρ=-0.385; p<0.001), which, on a single group level, could only be shown for the aMCI and AD group. There was significant correlation between MTA score with hippocampal and temporal lobe percentile. MTA score also correlated with Fazekas score (ρ=0.451; p<0.001) which again could only be detected within the aMCI and AD group. But there was no correlation between hippocampal percentile and total white matter lesion volume. When interpreting the MTA score, patient's age needs to be taken into consideration. Especially, in early dementia diagnostics, automated volumetric procedures might be advantageous, but due to the strong correlation of MTA score with hippocampal percentile, the MTA score still is a valid diagnostic marker. Whether hippocampal atrophy is modulated by cerebral small vessel disease still needs to be elucidated.

Marriage is associated with decreased lesion volumes and less brain atrophy in people with multiple sclerosis.

Married or long-term partnered patients with chronic diseases generally have better outcomes than unmarried patients, likely due to the potential for multifaceted support. However, the impact of marital status on multiple sclerosis (MS) radiographic disease burden is currently unknown. To compare total white matter hyperintensity lesion volumes, periventricular lesion volumes, and whole brain and grey matter volumes in married and unmarried people with MS (PwMS). We utilized multivariable linear regression to assess for differences in brain atrophy and lesion volumes between these two groups controlling for sex, MS disease duration in years, hypertension, history of smoking, alcohol consumption, history of depression and/or anxiety, and medication possession ratio (MPR). Married PwMS had significantly lower total lesion volumes (β = - 6.3, 95% CI - 12.1 to - 0.5, p = 0.033), lower PV lesion volumes (β = - 6.1, 95% CI - 11.7 to - 0.6, p = 0.030), higher normalized whole brain volumes (β = 38.3, 95% CI 6.0 to 70.7, p = 0.021), and higher normalized grey matter volumes (β = 20.9, 95% CI - 0.7 to 42.6, p = 0.058) than unmarried PwMS. Being married may be associated with improved MS outcomes as evidenced by decreased radiographic MS disease burden.

The apparent diffusion coefficient color Map for evaluating a large ischemic core.

Our previous work demonstrated that evaluating large ischemic cores using the apparent diffusion coefficient (ADC) could predict EVT outcomes, with the most frequent ADC (peak ADC) ≥520×10-6 mm2/s associated with better clinical results. Since the degree of ADC reduction reflects the severity of ischemic stress, this study aimed to assess the utility of an ADC color map in visualizing this stress. This retrospective cohort study included consecutive patients with a low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) using diffusion-weighted imaging (DWI) who underwent successful EVT recanalization between April 2014 and March 2023. To create a visual representation of ischemic stress, we assigned different colors to diffusion-weighted image (DWI) lesions based on their ADC values: ≥520×10-6 mm2/s, 520-440×10-6 mm2/s, and <440×10-6 mm2/s. We compared patients with peak ADC ≥520×10-6 mm2/s to those with lower peak ADC to identify factors associated with the higher value. A total of 78 patients were enrolled, with 34 having a peak ADC ≥520×10-6 mm2/s. The optimal ratio for discriminating peak ADC ≥520×10-6 mm2/s was found to be 60 % for the volume of the lesion with ADC ≥520×10-6 mm2/s (ADC520) relative to the total DWI lesion volume. This ratio demonstrated a sensitivity of 86 % and a specificity of 82 %. The ADC color map effectively portrays the depth of ischemic stress. A large ischemic core with an ADC520/DWI ratio >60 % may be salvageable with EVT. This approach offers a visual means for assessing EVT suitability in acute large ischemic stroke.

Association of Social Determinants of Health With Brain MRI Outcomes in Individuals With Pediatric Onset Multiple Sclerosis.

Accumulating evidence points to worse clinical outcomes among adults with multiple sclerosis (MS) belonging to minority or poverty-affected groups. By contrast, little is known about the outcomes of these populations with pediatric-onset MS (POMS). Individuals with POMS represent 5% of the MS population and are more racially diverse yet have been understudied regarding socioeconomic environment or characteristics. In this study, we investigated the association between childhood social determinants of health (SDOH) and brain MRI outcomes in patients with POMS. This is a retrospective single-site cohort study of patients with POMS with brain MRI quantitatively analyzed using icobrain software to yield total white matter lesion, black hole, whole brain, white matter, and gray matter volumes. All patients with POMS evaluated at New York University Langone MS Center and who underwent high-quality volumetric MRI scans were included in this study. SDOH indicators of race, ethnicity, health insurance type, parental education, and childhood neighborhood social vulnerability index (SVI) were examined for association with MRI outcomes using linear least absolute shrinkage selection operator penalized regression modeling. Disease-modifying therapy (DMT) timing and DMT efficacy were compared for each SDOH category. A total of 138 patients with POMS (70% female) were included with a mean age of 19.86 years and median disease duration of 4 years at time of scan. Public health insurance, Black race, Hispanic ethnicity, low parental education, and high SVI (greater neighborhood disadvantage) were each associated with white matter lesion and black hole volume. SVI was the strongest individual predictor of total white matter lesion (β = 4.63, p = 0.002) and black hole volume (β = 2.91, p = 0.003). In models incorporating all SDOH variables, public health insurance was the strongest predictor of total lesion (β = 2.48, p = 0.01) and black hole volume (β = 1.50, p = 0.02), attenuating the effect of SVI (β = 1.66, p = 0.33 and β = 1.00, p = 0.39). There were no differences in DMT timing or efficacy between categories of social disadvantage. Individual-level and neighborhood-level indicators of social disadvantage are associated with worse brain MRI outcomes in POMS. Further investigation of race, ethnicity, and childhood disadvantage as risk factors of MS susceptibility and severity is needed to reduce MS health disparities.

Verbal working memory and syntactic comprehension segregate into the dorsal and ventral streams, respectively.

Syntactic processing and verbal working memory are both essential components to sentence comprehension. Nonetheless, the separability of these systems in the brain remains unclear. To address this issue, we performed causal-inference analyses based on lesion and connectome network mapping using MRI and behavioural testing in two groups of individuals with chronic post-stroke aphasia. We employed a rhyme judgement task with heavy working memory load without articulatory confounds, controlling for the overall ability to match auditory words to pictures and to perform a metalinguistic rhyme judgement, isolating the effect of working memory load (103 individuals). We assessed non-canonical sentence comprehension, isolating syntactic processing by incorporating residual rhyme judgement performance as a covariate for working memory load (78 individuals). Voxel-based lesion analyses and structural connectome-based lesion symptom mapping controlling for total lesion volume were performed, with permutation testing to correct for multiple comparisons (4000 permutations). We observed that effects of working memory load localized to dorsal stream damage: posterior temporal-parietal lesions and frontal-parietal white matter disconnections. These effects were differentiated from syntactic comprehension deficits, which were primarily associated with ventral stream damage: lesions to temporal lobe and temporal-parietal white matter disconnections, particularly when incorporating the residual measure of working memory load as a covariate. Our results support the conclusion that working memory and syntactic processing are associated with distinct brain networks, largely loading onto dorsal and ventral streams, respectively.

Cotton swabs for the measurement of NF-ĸB, IFN-γ, and FOXP3+Treg from lesions of anogenital wart patients

BACKGROUND Local tissue immunity plays a significant role in anogenital warts’ (AGW) pathomechanism and persistence. Assessing biomarkers from lesions instead of serum is recommended to evaluate therapeutic response. Since biopsy is invasive, it is necessary to find less invasive and more comfortable methods. This study aimed to assess the reliability of cotton swabs and tape stripping for evaluating AGW’s lesions biomarkers. METHODS We compared cotton swab versus tape stripping method to quantify nuclear factor-κappaB (NF-ĸB), interferon-gamma (IFN-γ), and FOXP3+regulatory T cell (FOXP3+Treg) from 3 patients with AGW in the preliminary study. The method was selected based on contamination possibility, side effects, and a simpler approach. The main study examined 48 patients with AGW for reliability and reproducibility using the best sampling method from preliminary result and Spearman’s Rho analysis, while considering the HIV status and CD4+ counts. RESULTS Both cotton swabs and tape stripping obtained adequate protein content for biomarkers examination. However, the tape stripping method was causing serum contamination and painful for patients due to the stripping. The total lesion volume in cotton swab method was positively correlated with all patients’ NF-ĸB (p = 0.001). IFN-γ had a negative correlation in all reactive HIV patients (p = 0.012). FOXP3+Treg and CD4+ counts were negatively correlated with total volume in reactive HIV patients (p = 0.046 and 0.017, respectively). CONCLUSIONS The cotton swab method was reliable in examining NF-ĸB, IFN-γ, and FOXP3+Treg due to its convenience and lack of serum contamination from AGW lesions, potentially improving patient comfort and practical benefits.

PET-CT outcomes from a randomised controlled trial of rosuvastatin as an adjunct to standard tuberculosis treatment

Adjunctive rosuvastatin for rifampicin-susceptible pulmonary tuberculosis (rs-PTB) shows no effect on microbiological or radiological outcomes in a phase IIb randomised, controlled trial (NCT04504851). We explore the impact of adjunctive rosuvastatin on 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) imaging in a sub-study of 24 participants. Changes in standardised uptake value (SUVmax, SUVmean), Total Metabolic Volume, (TMV), Total Lesion Glycolysis (TLG), cavity diameter and volume, between week 0 and week 8 post-randomisation, are evaluated. Here we show no evidence of difference in the reduction in TLG [median 65.8% for the rosuvastatin group (Q1, Q3 38.6, 94.5) vs 64.3% for standard tuberculosis treatment group (Q1, Q3 −20.0, 81.7), P = 0.32], reduction in cavity volume on CT [median 3.2 cm3 (IQR 11.1, 0.5) for rosuvastatin, 2.2 cm3 (IQR 4.6, 0.7) for control (p = 0.72)], or any other PET-CT parameter measured. We show that the first 8-weeks of standard tuberculosis treatment results in a reduction in the volumetric indices (TLG and TMV), but had little change in SUVmax or SUVmean. Change in TLG and TMV holds promise as biomarkers of tuberculosis treatment response: future PET-CT studies should evaluate their role in predicting relapse-free cure, and the overall role of 18F-FDG-PET-CT as a tool for early-phase tuberculosis clinical trials.

Frailty reduces penumbral volumes and attenuates treatment response in hyperacute ischemic stroke.

Frailty-the loss of physiological reserve to withstand a stressor event-is associated with poorer outcomes following acute stroke reperfusion therapies. However, the mechanisms underlying this relationship are poorly understood. This study investigated the association between frailty and penumbral volumes in hyperacute ischemic stroke. Total ischemic lesion volumes (comprising infarct core and penumbral volumes) were measured using computed tomography (CT) perfusion imaging to give the penumbral fraction within the ischemic lesion. Pre-stroke frailty was measured using a validated frailty index. The relationship between frailty and penumbral fraction was adjusted for age, onset-to-CT interval, collateral scores, small vessel disease burden and vascular comorbidities. Stroke severity was measured using the National Institutes of Health Stroke Scale at baseline and after 24h. In 55 individuals receiving thrombolysis for ischemic stroke, increasing frailty was associated with a reduction in penumbral fraction (rs = -0.36, P < 0.01). This remained significant after adjustment for age, onset-to-imaging time and collateral score (beta = -1.16, P < 0.001). Correspondingly, frailty was independently negatively associated with proportional improvement in stroke severity following treatment (beta = -2.00, P < 0.01). C-reactive protein (CRP) on presentation was associated with frailty index (rs = 0.38, P < 0.01) and penumbral fraction (rs = -0.30, P = 0.02). A reduction in salvageable penumbra in frailty may explain the treatment-attenuating effects of frailty on reperfusion therapies. The association with CRP motivates further research into a possible inflammatory component of this relationship. Frailty is independently associated with reduced penumbra and poorer neurological recovery in acute stroke. These findings may explain the attenuated response to stroke reperfusion therapies seen in frailer individuals.

The effect of total size, area, and volume of lesions in multifocal/multicentric breast cancers and unifocal breast cancers on survival: An observational study.

In this study, we aimed to investigate the prognostic effect of the classifications made according to the stage of the largest lesion diameter (T-max stage) and of the sum of the longest diameters of the lesions (T-sum stage), the largest area stage (A-max stage), the sum of the largest areas (A-sum stage), the highest volume stage (V-max stage), the sum of the highest volume (V-sum stage) on disease-free survival, and overall survival (OS) in multifocal/multicentric breast cancers (MMBCs) and unifocal breast cancers (UBCs). The study included a total of 769 patients either with MMBC (n = 128) or UBC (n = 641) who underwent surgery between 2006 and 2015. In the analysis, the median age of 769 patients was 53.0 (20.0-94.0) years, and 16.6% of these 769 patients were MMBC and 83.4% were UBC. In multivariate analysis, lymphovascular invasion (LVİ), estrogen receptor, and nodal status were common independent prognostic factors, whereas T-max stage [(HR: 1.17) (CI 95%: 1.03-1.33) (P = .018)] was a prognostic factor for OS. In multivariate analysis, the T-max stage is an independent risk factor for OS. Therefore, T-max should be continued to be used for measurement and T-stage should be used for classification in MMBCs/UBCs.

Cerebrovascular pulsatility indicates preoperative subcortical cognitive impairment and an increased risk for postoperative delirium in elderly patients undergoing elective spine surgery.

Advances in spine surgery enable safe interventions in elderly patients, but perioperative neurocognitive disorders (pNCD), such as post-operative delirium (POD) and cognitive dysfunction (POCD), remain a serious concern. Pre-operative cognitive impairment is a major risk factor for pNCD. Comprehensive pre-operative cognitive assessments are not feasible in clinical practice, making effective screening methods desirable. This study investigates whether pre-operative cerebrovascular duplex sonography can assess subcortical (vascular) cognitive impairment and the risk for POD. This prospective single-center study recruited patients aged ≥60 years scheduled for elective spine surgery at a German university hospital. Patients underwent pre-operative assessments including cognitive abilities (CERAD test battery), structural MRI, and cerebrovascular duplex sonography. POD screening was conducted three times daily for at least 3 days. The primary hypothesis, that the mean pulsatility index (PI) of both internal carotid arteries (ICA) predicts POD risk, was tested using logistic regression. Secondary analyses examined the association between POD risk and ICA flow (time-averaged peak velocities, TAPV) and correlations with cognitive profiles and MRI characteristics. POD occurred in 22% of patients (n = 22/99) within three postoperative days. Patients with POD were significantly older (75.9 ± 5.4 vs. 70.0 ± 6.9 years, p < 0.01) but did not differ by gender (p = 0.51). ICA PI significantly predicted POD risk (OR = 5.46 [95%CI: 1.81-16.49], p = 0.003), which remained significant after adjustment for age and duration of surgery (ORadj = 6.38 [95% CI: 1.77-23.03], p = 0.005). TAPV did not inform the POD risk (p = 0.68). ICA PI Pre-operative cognitive scores were significantly associated with ICA PI (mean CERAD score: r = -0.32, p < 0.001). ICA PI was also significantly associated with total white matter lesion volume (τ = 0.19, p = 0.012) and periventricular white matter lesion volume (τ = 0.21, p = 0.007). This is the first study to demonstrate that cerebrovascular duplex sonography can assess the risk for POD in elderly spine surgery patients. Increased ICA PI may indicate subcortical impairment, larger white matter lesion load, and lower white matter volume, predisposing factors for POD. Pre-operative cerebrovascular duplex sonography of the ICA is widely available, easy-to-use, and efficient, offering a promising screening method for POD risk. Increased ICA PI could supplement established predictors like age to adjust surgical and peri-operative procedures to individual risk profiles.

Nd-YAG laser-assisted pulmonary metastasectomy: initial experience from a tertiary care cancer center in India.

Pulmonary metastasectomy is recommended for metastatic lung lesions when R0 resection is possible, the primary site is in controlled status, surgery is of low risk, and extrathoracic metastases are absent. We present the initial experiences of laser-assisted surgery (LAS) for pulmonary metastatic lesions from a tertiary care cancer center in India. All patients undergoing non-anatomical pulmonary metastasectomy between September 2022 and January 2023 for synchronous and metachronous lesions, operated on by a single consultant thoracic oncosurgeon in a tertiary care center of India, were identified from a prospective database. Ten patients with 124 metastatic lesions were included in the study. A hybrid approach (video-assisted thoracoscopic surgery (VATS) with mini-thoracotomy) was performed. Measurements of total lesion volume and lung parenchyma resected were taken from the final histopathological analysis of the intraoperative sample. LAS was performed for 102 lesions and stapled wedge resection for 22 lesions. Evidence of malignancy was noted in 88/102 (86.3%) of the lesions excised. Patients with LAS had advantages of parenchyma preservation, less postoperative morbidities, and shorter hospital stays. LAS of pulmonary metastatic lesions addresses more lesions in a single sitting; the bilateral lung lesions can be operated and has parenchyma preserving and good sealant properties. The online version contains supplementary material available at 10.1007/s12055-024-01723-8.

Impact of repositioning on brain injury following transcatheter aortic valve replacement with a self-expanding valve

Repositionable self-expanding valves allow for repositioning during deployment to achieve optimal valve placement. However, the risk of brain injury associated with repositioning, as detected by diffusion-weighted magnetic resonance imaging (DW-MRI), is unknown. Consecutive patients undergoing transcatheter aortic valve replacement (TAVR) with repositionable self-expanding valves and receiving DW-MRI before and within 7 days post-TAVR procedure were included. The primary outcomes were incidence, number, total volume, and volume per lesion of the cerebral ischemic lesion in DW-MRI after TAVR. Univariate and multivariate logistic regression assessed the association between repositioning and bigger total lesion volume (> 1 cm3 or > 0.5 cm3). Negative binomial regressions were performed to explore the association between repositioning and number of lesions. A propensity score matching was performed to adjust the potential confounders. Moreover, inverse probability of treatment weighted regression model with nonstabilized weights was used as sensitivity analysis. Among 243 included patients, repositioning was performed in 116 (47.7%) patients. The incidence of overt stroke (1.7% vs. 1.6%, p = 0.927) and silent stroke (86.2% vs. 85.8%, p = 0.932) were comparable between two groups. However, the number of new lesions (5.0 [2.0–9.0] vs. 3.0 [2.0–6.0], p = 0.048), and total lesion volume (275.0 [90.0–947.5] mm3 vs. 180.0 [50.0–440.0] mm3, p = 0.022) were significantly higher in the repositioned group. Moreover, the proportion of patients with lesion size greater than 0.5 cm3 was higher in the repositioned group (37.9% vs. 22.0%, p = 0.007). The similar results were observed after propensity score matching. In both multivariate regression model and sensitivity analysis, the repositioning was the independent predictor of number of lesions and bigger total lesion volume after TAVR. The utilization of the repositioning feature may increase the number and volume of silent brain infarcts in DW-MRI in patients who underwent TAVR. (Transcatheter Aortic Valve Replacement Single Center Registry in Chinese Population [TORCH]; NCT02803294)

Structural and molecular imaging-based characterization of soft tissue and vascular calcification in hyperphosphatemic familial tumoral calcinosis.

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare disorder caused by deficient FGF23 signaling and resultant ectopic calcification. Here, we systematically characterized and quantified macro- and micro-calcification in a HFTC cohort using CT and 18F-sodium fluoride PET/CT (18F-NaF PET/CT). Fourier-transform infrared (FTIR) spectroscopy was performed on 4 phenotypically different calcifications from a patient with HFTC, showing the dominant component to be hydroxyapatite. Eleven patients with HFTC were studied with CT and/or 18F-NaF PET/CT. Qualitative review was done to describe the spectrum of imaging findings on both modalities. CT-based measures of volume (eg, total calcific burden and lesion volume) and density (Hounsfield units) were quantified and compared to PET-based measures of mineralization activity (eg, mean standardized uptake values-SUVs). Microcalcification scores were calculated for the vasculature of 6 patients using 18F-NaF PET/CT and visualized on a standardized vascular atlas. Ectopic calcifications were present in 82% of patients, predominantly near joints and the distal extremities. Considerable heterogeneity was observed in total calcific burden per patient (823.0 ± 670.1cm3, n = 9) and lesion volume (282.5 ± 414.8cm3, n = 27). The largest lesions were found at the hips and shoulders. 18F-NaF PET offered the ability to differentiate active vs quiescent calcifications. Calcifications were also noted in multiple anatomic locations, including brain parenchyma (50%). Vascular calcification was seen in the abdominal aorta, carotid, and coronaries in 50%, 73%, and 50%, respectively. 18F-NaF-avid, but CT-negative calcification was seen in a 17-year-old patient, implicating early onset vascular calcification. This first systematic assessment of calcifications in a cohort of patients with HFTC has identified the early onset, prevalence, and extent of calcification. It supports 18F-NaF PET/CT as a clinical tool for distinguishing between active and inactive calcification, informing disease progression, and quantification of ectopic and vascular disease burden.

Perihaematomal Oedema Evolution over 2 Weeks after Spontaneous Intracerebral Haemorrhage and Association with Outcome: A Prospective Cohort Study.

We know little about the evolution of perihaematomal oedema (PHO) &gt;24 h after ICH onset. We aimed to determine the trajectory of PHO after ICH onset and its association with outcome. We did a prospective cohort study using a pre-specified scanning protocol in adults with first-ever spontaneous ICH and measured absolute PHO volumes on CT head scans at ICH diagnosis and 3 ± 2, 7 ± 2, and 14 ± 2 days after ICH onset. We used the largest ICH if ICHs were multiple. The primary outcomes were (a) the trajectory of PHO after ICH onset and (b) the association between PHO (absolute volume at the time when most repeat CT head scans were obtained, and change in PHO volume at this time compared with the first CT head scan) and poor functional outcome (modified Rankin scale 3-6 at 90 days). We pre-specified multivariable logistic regression models of this association adjusting analyses for potential confounders: age, GCS, infratentorial ICH location, and intraventricular extension. In 106 participants of whom 49 (46%) were female, with a median ICH volume 7 mL (interquartile range [IQR] 2-22 mL), the trajectory of median PHO volume increased from 14 mL (IQR: 7-26 mL) at diagnosis to 18 mL (IQR: 8-40 mL) at 3 ± 2 days (n = 87), 20 mL (IQR: 8-48 mL) at 7 ± 2 days (n = 93) and 21 mL (IQR: 10-54 mL) at 14 ± 2 days (n = 78) (p = &lt;0.001). PHO volume at each time point was collinear with ICH volume at diagnosis (│r│ &gt;0.7), but the change in PHO volume between diagnosis and each time point was not. Given collinearity, we used total lesion (i.e., ICH + PHO) volume instead of PHO volume in a logistic regression model of its association at each time point with outcome. Increasing total lesion (ICH + PHO) volume at day 7 ± 2 was associated with poor functional outcome (adjusted OR per mL 1.02, 95% CI: 1.00-1.03; p = 0.036), but the increase in PHO volume between diagnosis and day 7 ± 2 was not associated with poor functional outcome (adjusted OR per mL 1.03, 95% CI: 0.99-1.07; p = 0.132). PHO volume increases throughout the first 2 weeks after onset of mild to moderate ICH. Total lesion (ICH + PHO) volume at day 7 ± 2 was associated with poor functional outcome, but the change in PHO volume between diagnosis and day 7 ± 2 was not. Prospective cohort studies with larger sample sizes are needed to investigate these associations and their modifiers.

The association of structural versus load-dependent large artery stiffness mechanisms with cerebrovascular damage and cortical atrophy in humans.

Large central arterial stiffness is a risk factor for cerebrovascular damage and subsequent progression of neurodegenerative diseases, including Alzheimer's disease and dementia. However, arterial stiffness is determined by both the intrinsic components of the arterial wall (structural stiffness) and the load (i.e., arterial blood pressure) exerted upon it by the blood (load-dependent stiffness). This study aimed to determine the degree to which structural and/or load-dependent mechanisms of central arterial stiffness are associated with cerebrovascular damage. Among 128 healthy individuals (aged 63±6, age range: 50-80 years, 42% men), aortic and carotid artery stiffness was measured via carotid-femoral pulse wave velocity and B-mode ultrasonography, respectively. Using participant-specific exponential models, both aortic and carotid artery stiffness were standardized to a reference blood pressure to separate their structural and load-dependent stiffness mechanisms. Magnetic resonance imaging was used to derive total, periventricular, and deep cerebral white matter lesion volume (WMLV) and global cortical thickness. After adjusting for common cardiovascular disease risk factors, a 1 m/s increase in structural aortic stiffness was associated with 15% greater total WMLV (95% confidence interval [CI] = 0.01, 0.27, P = 0.036), 14% greater periventricular WMLV (95%CI = 0.004, 0.25, P = 0.044) and 0.011mm lower cortical thickness (95%CI = -0.022, -1.18, P = 0.028). No association was observed between structural carotid stiffness and WMLVs (total, periventricular, and deep), and neither aortic nor carotid load-dependent stiffness was associated with WMLVs or cortical thickness. Structural, not load-dependent, mechanisms of aortic stiffness are related to cerebrovascular-related white matter damage.

Automatic lesion detection at Multiple Sclerosis patients – Comparison of 2D- and 3D-FLAIR-datasets

BackgroundMultiple Sclerosis (MS) is a common autoimmune inflammatory disease of the central nervous system (CNS). Magnetic Resonance Imaging (MRI) allows a sensitive assessment of the CNS and is established for diagnostic, prognostic and (therapy-) monitoring purposes. Especially lesion counting in T2- or Fluid Attenuated Inversion Recovery (FLAIR)-weighted images plays a decisive role in clinical routine. Software-packages allowing an automatic evaluation of image data are increasingly established aiming a faster and improved workflow. These programs allow e.g. the counting, spatial attribution and volumetry of MS-lesions in FLAIR-weighted images. Research has shown that 3D-FLAIR-sequences are superior to 2D-FLAIR-sequences in visual evaluation of lesion burden in MS. An influence on the automatic analysis is expectable but not yet systematically studied. This work will therefore investigate the influence of 2D- and 3D datasets on the results of an automatic assessment. Material and methodsIn this prospective study, 80 Multiple Sclerosis patients underwent a clinically indicated routine MRI examination. The clinical routine protocol already including a 3D-FLAIR sequence was adapted by an additional 2D-FLAIR sequence also conform to the 2021 MAGNIMS-CMSCNAIMS consensus recommendations. To obtain a quantitative analysis for assessment of amount, dissemination and volume of the lesions, the acquired MR images were post-processed using the CE-certified Software mdbrain (mediaire, Berlin, Germany). The resulting data were statistically analysed using the paired t-test for normally distributed data and the Wilcoxon-signed-rank-test for not normally distributed data respectively. Demographic data and data such as the subtype, duration, severity and therapy of the disease were collected, pseudonymized and evaluated. ResultsThere is a significant difference concerning the total number and lesion volume with more lesions being detected (2D: 29.7, +/- 20.22 sd; 3D: 40.1 +/- 31.67 sd; p < 0.0001) but lower total volume (2D: 6.24 +/- 6.11 sd; 3D: 5.39 +/- 6.37 sd; p < 0.0001) when using the 3D- sequence. Especially significantly more small lesions in the unspecific white matter and infratentorial region were detected by using the 3D-FLAIR sequence (p < 0.0001) compared to the 2D-FLAIR image. Main reason for the lower total volume in the 3D-FLAIR sequence was the calculated volume for periventricular lesions which was significantly beneath the calculated volume from the 2D-FLAIR sequence (p < 0.0001). ConclusionAutomatic lesion counting and volumetry is feasible with both 2D- and 3D-weightend FLAIR images. Still, it leads to partly significant differences even between two sequences that both are conform to the 2021 MAGNIMS-CMSCNAIMS consensus recommendations. This study contributes valuable insights into the impact of using different input data from the same patient for automated MS lesion evaluation.

Brain lesion microstructure in neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein disease.

Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) diagnosis are based on the presence of serological and magnetic resonance imaging (MRI) biomarkers. Diffusion tensor imaging (DTI), neurites orientation dispersion and density imaging (NODDI), and the Spherical Mean Technique (SMT) may be helpful to provide a microstructural characterization of the different types of white matter lesions and give an insight about their different pathological mechanisms. The aim of the study was to characterize microstructural differences between brain typical lesions (TLs) and nontypical lesions (nTLs). A total of 17 NMOSD and MOGAD patients [9 Aquaporin4 (AQP4)+NMO, 2 seronegative-NMO, 6 MOGAD] underwent MRI scans on a 3 Tesla MAGNETON PRISMA. Diffusion parameters (fractional anisotropy; mean diffusivity [MD]; intracellular volume fraction [ICVF]; extra-neurite transverse diffusivity; and extra-neurite MD; neurite signal fraction) were obtained using DTI, NODDI, and SMT. Microstructural parameters within lesions were compared through a generalized linear model using age, sex, and total lesion volume as covariates. In NMOSD/MOGAD whole cohort (total lesions=477), TLs showed increased MD and decreased ICVF compared to nTLs (p<.05), indicating higher inflammation and axonal loss. Similar results were found also in the AQP4+NMO subgroup (decreased ICVF, p<.05). Furthermore, in NMOSD/MOGAD whole cohort and in AQP4+NMO subgroup, TLs showed a trend toward higher EXRATRANS than nTLs, suggesting a more severe degree of demyelination within TLs. TLs and nTLs in NMOSD/MOGAD showed different diffusion MRI-derived microstructural features, with TLs showing a more severe degree of inflammation and fiber disruption with respect to nTLs.

Different extramedullary disease shown in chemokine receptor 4 targeted PET/CT with [ 68 Ga]Ga-pentixafor in patients with Waldenström macroglobulinemia and smoldering disease.

It is important to distinguish Waldenström macroglobulinemia from smoldering Waldenström macroglobulinemia (sWM), because only patients with Waldenström macroglobulinemia require treatment, however the distinction can be clinically complex. The aim of this study is to investigate whether [ 68 Ga]Ga-pentixafor PET/CT shows different characteristics in sWM and Waldenström macroglobulinemia patients and therefore can help to differentiate Waldenström macroglobulinemia and sWM. Thirty-seven patients with newly diagnosed Waldenström macroglobulinemia and 11 sWM patients were analyzed [35 men and 13 women; 64.3 ± 10.7 (range, 29-87) years old]. The SUV max of bone marrow disease, lymph nodes, and other extramedullary diseases on [ 68 Ga]Ga-pentixafor were significantly higher than those on 2-[ 18 F]FDG PET/CT ( P < 0.05). On [ 68 Ga]Ga-pentixafor PET/CT, patients with Waldenström macroglobulinemia had more lymph node regions involved, significantly higher incidence of involvement in more than three lymph node regions, larger nodal disease, and higher incidence of other extramedullary disease when compared with sWM patients ( P < 0.05). Waldenström macroglobulinemia patients showed significantly higher total lesions uptake, total lesion volume, and SUV max of extramedullary disease than sWM patients did ( P < 0.05). None of the visual or semiquantitative indexes in 2-[ 18 F]FDG PET/CT showed significant difference between Waldenström macroglobulinemia and sWM patients. [ 68 Ga]Ga-pentixafor PET/CT had better diagnostic performance than 2-[ 18 F]FDG PET/CT in Waldenström macroglobulinemia. Patients with Waldenström macroglobulinemia presented with more extensive extramedullary disease shown in [ 68 Ga]Ga-pentixafor PET/CT than sWM patients did.

Neighborhood disadvantage is associated with working memory and hippocampal volumes among older adults

ABSTRACT It is not well understood how neighborhood disadvantage is associated with specific domains of cognitive function and underlying brain health within older adults. Thus, the objective was to examine associations between neighborhood disadvantage, brain health, and cognitive performance, and examine whether associations were more pronounced among women. The study included 136 older adults who underwent cognitive testing and MRI. Neighborhood disadvantage was characterized using the Area Deprivation Index (ADI). Descriptive statistics, bivariate correlations, and multiple regressions were run. Multiple regressions, adjusted for age, sex, education, and depression, showed that higher ADI state rankings (greater disadvantage) were associated with poorer working memory performance (p < .01) and lower hippocampal volumes (p < .01), but not total, frontal, and white matter lesion volumes, nor visual and verbal memory performance. There were no significant sex interactions. Findings suggest that greater neighborhood disadvantage may play a role in working memory and underlying brain structure.

Association between renal insufficiency and lesion characteristics of posterior reversible encephalopathy syndrome.

Posterior reversible encephalopathy syndrome (PRES) is characterized by cerebral blood flow dysregulation and the blood-brain barrier (BBB) disruption. While renal insufficiency has been considered a factor in BBB fragility, the relationship between renal insufficiency and the PRES lesions volume remains unclear. This observational study was performed retrospectively. PRES patients were categorized into two groups with renal insufficiency, defined as an estimated glomerular filtration rate (eGFR) of less than 60mL/min/1.73m2 on the day of symptom occurrence. Lesion volume was measured using fluid-attenuated inversion recovery (FLAIR) imaging, and the brain was divided into nine regions. The volume of the parietal-occipital-temporal lobe was considered typical, while the other six regions were labeled as atypical. The study included 200 patients, of whom 94 (47%) had renal insufficiency. Patients with renal insufficiency had a larger lesion volume (144.7 ± 125.2cc) compared to those without renal insufficiency (110.5 ± 93.2cc; p = 0.032); particularly in the atypical lesions volume (49.2 ± 65.0 vs. 29.2 ± 44.3cc; p = 0.013). However, there was no difference in the reversibility of the lesions (35.2 ± 67.5 vs. 18.8 ± 33.4cc; p = 0.129). Multiple regression analysis revealed that decreases in eGFR (β = -0.34, 95% CI -0.62-0.05, p = 0.020) were positively associated with total lesion volume. Our findings suggest that PRES patients with renal insufficiency experience more severe lesion volumes, likely due to the atypical brain regions involvement. The lesions involving atypical regions may have a similar pathophysiology to typical lesions, as the PRES lesions reversibility was found to be similar between individuals with and without renal insufficiency.