3D MPRAGE Research Articles

Osteopontin levels are associated with late-time lower regional brain volumes in multiple sclerosis

Osteopontin (OPN) is a proinflammatory marker produced by systemic immune and central nervous system (CNS) resident cells. We examined, if the level of OPN in the cerebrospinal fluid (CSF) and blood is associated with late-time regional brain volumes and white matter (WM) lesion load in MS. Concentrations of OPN in blood and CSF were related to MRI findings 10.1 ± 2.0 years later in 46 patients with MS. OPN concentration was measured by ELISA, while regional brain volumes and lesion load was assessed by magnetic resonance imaging (MRI) using 3D MPRAGE sequence and automated MR volumetry. OPN measured in the CSF was associated with several regional brain volumes and WM lesion load measured 10.1 ± 2.0 years later. CSF OPN concentration correlated with long-term enlargement of lateral- and inferior lateral ventricles and the elevation of gross CSF volume, in conjunction with the reduction of several cortical/subcortical gray matter and WM volumes. Serum OPN showed no long-term association with regional brain volumes. OPN measured from the CSF but not from the serum was associated with lower regional brain volumes measured a decade later, indicating the primary role of inflammation within the CNS in developing long-term brain related alterations.

Cortical Thinning and White Matter Loss in Sickle Cell Anemia Despite Chronic Exchange Transfusion Therapy

Neurovascular complications are a common and major cause of morbidity and mortality in patients with sickle cell disease (SCD). Prior studies have demonstrated cortical thinness (Kim et al. 2016) as well as reduced cerebral volume in children with SCD (Kawadler et al. 2013) when compared to age-matched controls. There is very limited data regarding cerebral volume in adults with SCD. Recently, our group showed that adults with SCD have reduced cerebral volumes when compared to race and age-matched controls (Santini et al. 2021a). A prior prospective study by Nitkunan et al. 2011. demonstrated brain atrophy rate of −0.914%±0.8% in older adults (mean 68 years old) with Small Vessels Disease, which is about twice the rate of healthy controls. Transfusion therapy has been effective in the primary and secondary prevention of strokes and silent infarcts in SCD. Automated erythrocytapheresis (exchange transfusion), in particular, is the most aggressive disease modifying-treatment in SCD, by rapidly diluting sickle hemoglobin and replacing it with normal hemoglobin. We hereby present a case of a 42 -year-old woman with sickle cell anemia (HbSS) who developed accelerated loss of cerebral volume within a three-year period despite chronic exchange transfusion therapy. The patient underwent brain MRI in 2016 and 2019 as part of an NIH-funded, prospective, longitudinal study of the neuroradiological correlates of cognitive dysfunction in SCD. Past medical history is notable for prior right hemispheric stroke for which she was placed on chronic exchange transfusion monthly with the goal of reducing HbS to <30%. T1-weighted images were acquired at 7T MRI using a customized RF coil (Santini et al. 2021b) and with the following parameters: 3D MPRAGE, TE/TI/TR = 2.17/1200/3000 ms, resolution 0.75 mm isotropic, total acquisition time = 5 min. The extent of atrophy was estimated using the longitudinal analysis as part of the Freesurfer package (version 7.1.1) and ITK-snap (version 3.8.0). The pre-exchange HbS was reliably maintained <30% throughout the observation period, during which the patient did not develop new strokes or neurological complications. Unfortunately, in spite of the patient's excellent adherence with the treatment and the achievement of the target HbS values, we observed progression of cerebral atrophy of 2.47% in volume in the hemisphere contralateral to the stroke between the two time points. The differences are also visible in the raw data (Figure 1). Chronic exchange transfusion is the most aggressive preventive treatment for the neurological sequelae of sickle cell disease. This case demonstrates an accelerated brain atrophy, suggesting that this treatment may not be fully protective against progressive cerebral atrophy. Unfortunately, the mechanism of brain atrophy in SCD is not fully understood. More longitudinal studies are needed to assess cortical changes and cerebral volume changes as this can lead to further understanding of their pathophysiology and to the development of therapeutic options to arrest the progression of cerebrovascular disease in this population. [Display omitted] DisclosuresNovelli: Novartis Pharmaceuticals: Consultancy.

Whole brain and deep gray matter structure segmentation: Quantitative comparison between MPRAGE and MP2RAGE sequences.

T1-weighted MRI images are commonly used for volumetric assessment of brain structures. Magnetization prepared 2 rapid gradient echo (MP2RAGE) sequence offers superior gray (GM) and white matter (WM) contrast. This study aimed to quantitatively assess the agreement of whole brain tissue and deep GM (DGM) volumes obtained from MP2RAGE compared to the widely used MP-RAGE sequence. Twenty-nine healthy participants were included in this study. All subjects underwent a 3T MRI scan acquiring high-resolution 3D MP-RAGE and MP2RAGE images. Twelve participants were re-scanned after one year. The whole brain, as well as DGM segmentation, was performed using CAT12, volBrain, and FSL-FAST automatic segmentation tools based on the acquired images. Finally, contrast-to-noise ratio between WM and GM (CNRWG), the agreement between the obtained tissue volumes, as well as scan-rescan variability of both sequences were explored. Significantly higher CNRWG was detected in MP2RAGE vs. MP-RAGE (Mean ± SD = 0.97 ± 0.04 vs. 0.8 ± 0.1 respectively; p<0.0001). Significantly higher total brain GM, and lower cerebrospinal fluid‏ volumes were obtained from MP2RAGE vs. MP-RAGE based on all segmentation methods (p<0.05 in all cases). Whole-brain voxel-wise comparisons revealed higher GM tissue probability in the thalamus, putamen, caudate, lingual gyrus, and precentral gyrus based on MP2RAGE compared with MP-RAGE. Moreover, significantly higher WM probability was observed in the cerebellum, corpus callosum, and frontal-and-temporal regions in MP2RAGE vs. MP-RAGE. Finally, MP2RAGE showed a higher mean percentage of change in total brain GM compared to MP-RAGE. On the other hand, MP-RAGE demonstrated a higher overtime percentage of change in WM and DGM volumes compared to MP2RAGE. Due to its higher CNR, MP2RAGE resulted in reproducible brain tissue segmentation, and thus is a recommended method for volumetric imaging biomarkers for the monitoring of neurological diseases.

Long-term Anabolic–Androgenic Steroid Use Is Associated With Deviant Brain Aging

BackgroundHigh-dose long-term use of anabolic–androgenic steroids (AASs) may cause a range of adverse effects, including brain and cognitive abnormalities. We performed age prediction based on brain scans to test whether prolonged AAS use is associated with accentuated brain aging. MethodsT1-weighted magnetic resonance imaging (3D MPRAGE [magnetization-prepared rapid acquisition gradient-echo]) scans were obtained from male weightlifters with a history of prolonged AAS use (n = 130) or no AAS use (n = 99). We trained machine learning models on combinations of regional brain volumes, cortical thickness, and surface area in an independent training set of 1838 healthy male subjects (18–92 years of age) and predicted brain age for each participant in our study. Including cross-sectional and longitudinal (mean interval = 3.5 years, n = 76) magnetic resonance imaging data, we used linear mixed-effects models to compare the gap between chronological age and predicted brain age (the brain age gap [BAG]) for the two groups and tested for group differences in the rate of change in BAG. We tested for associations between apparent brain aging and AAS use duration, pattern of administration, and dependence. ResultsAAS users had higher BAG compared with weightlifting control subjects, which was associated with dependency and longer history of use. Group differences in BAG could not be explained by other substance use, general cognitive abilities, or depression. While longitudinal analysis revealed no evidence of increased brain aging in the overall AAS group, accelerated brain aging was seen with longer AAS exposure. ConclusionsThe findings suggest that long-term high-dose AAS use may have adverse effects on brain aging, potentially linked to dependency and exaggerated use of AASs.

Do High Mental Demands at Work Protect Cognitive Health in Old Age via Hippocampal Volume? Results From a Community Sample.

As higher mental demands at work are associated with lower dementia risk and a key symptom of dementia is hippocampal atrophy, the study aimed at investigating the association between mental demands at work and hippocampal volume. We analyzed data from the population-based LIFE-Adult-Study in Leipzig, Germany (n = 1,409, age 40–80). Hippocampal volumes were measured via three-dimensional Magnetic resonance imaging (MRI; 3D MP-RAGE) and mental demands at work were classified via the O*NET database. Linear regression analyses adjusted for gender, age, education, APOE e4-allele, hypertension, and diabetes revealed associations between higher demands in “language and knowledge,” “information processing,” and “creativity” at work on larger white and gray matter volume and better cognitive functioning with “creativity” having stronger effects for people not yet retired. Among retired individuals, higher demands in “pattern detection” were associated with larger white matter volume as well as larger hippocampal subfields CA2/CA3, suggesting a retention effect later in life. There were no other relevant associations with hippocampal volume. Our findings do not support the idea that mental demands at work protect cognitive health via hippocampal volume or brain volume. Further research may clarify through what mechanism mentally demanding activities influence specifically dementia pathology in the brain.

Prognostic relevance of temporal muscle thickness as a marker of sarcopenia in patients with glioblastoma at diagnosis.

Temporal muscle thickness (TMT) is a surrogate marker of sarcopenia, correlated with survival expectancy in patients suffering from brain metastases and recurrent or treated glioblastoma. We evaluated the prognostic relevance of TMT measured on brain MRIs acquired at diagnosis in patients affected by glioblastoma. We retrospectively enrolled 51 patients in our Institution affected by methylated MGMT promoter, IDH1-2 wild-type glioblastoma, who underwent complete surgical resection and subsequent radiotherapy with concomitant and maintenance temozolomide, from January 1, 2015, to April 30, 2017. The last clinical/radiological follow-up date was set to September 3, 2019. TMT was measured bilaterally on reformatted post-contrast 3D MPRAGE images, acquired on our 3-T scanner no more than 2days before surgery. The median, 25th, and 75th percentile TMT values were identified and population was subdivided accordingly; afterwards, statistical analyses were performed to verify the association among overall survival (OS) and TMT, sex, age, and ECOG performance status. In our cohort, the median OS was 20months (range 3-51). Patients with a TMT ≥ 8.4mm (median value) did not show a statistically significant increase in OS (Cox regression model: HR 1.34, 95% CI 0.68-2.63, p = 0.403). Similarly, patients with a TMT ≥ 9.85mm (fourth quartile) did not differ in OS compared to those with TMT ≤ 7mm (first quartile). The statistical analyses confirmed a significant association among TMT and sex (p = 0.0186), but none for age (p = 0.642) and performance status (p = 0.3982). In our homogeneous cohort of patients with glioblastoma at diagnosis, TMT was not associated with prognosis, age, or ECOG performance status. • Temporal muscle thickness (TMT) is a surrogate marker of sarcopenia and has been correlated with survival expectancy in patients suffering from brain metastases and recurrent or treated glioblastoma. • We appraised the correlation among TMT and survival, sex, age at surgery, and performance status, measured on brain MRIs of patients affected by glioblastoma at diagnosis. • TMT did not show any significant correlation with prognosis, age at surgery, or performance status, and its usefulness might be restricted only to patients with brain metastases and recurrent or treated glioblastoma.

Gadolinium-Enhanced 3D T1-Weighted Black-Blood MR Imaging for the Detection of Acute Optic Neuritis.

A 3D T1-weighted black-blood sequence was recently shown to improve the detection of contrast-enhancing lesions in the brain in patients with MS compared with a 3D T1-weighted MPRAGE sequence. We compared a contrast-enhanced 3D T1-weighted black-blood sequence with a dedicated orbital contrast-enhanced T1-weighted Dixon sequence in patients with acute optic neuritis. MR imaging data (3T) of 51 patients showing symptoms of acute optic neuritis were analyzed retrospectively, including whole-brain contrast-enhanced 3D T1-weighted black-blood and dedicated orbital coronal 2D or 3D contrast-enhanced T1-weighted Dixon sequences. Two neuroradiologists assessed the images for overall image quality, artifacts, diagnostic confidence, and visual contrast enhancement. Furthermore, the standardized contrast-to-noise ratio was calculated. The final diagnosis of acute optic neuritis was established on the basis of clinical presentation, visually evoked potentials, and optical coherence tomography. Thirty of 51 patients were diagnosed with acute optic neuritis. Of those, 21 showed contrast-enhancing lesions in the optic nerves, similarly detectable on contrast-enhanced T1-weighted Dixon and contrast-enhanced T1-weighted black-blood images. Thus, the accuracy for each sequence was identical, with a resulting sensitivity of 70% and specificity of 90% or 100% (depending on the reader). Overall image quality, diagnostic confidence, visual contrast enhancement, and artifacts were rated similarly in contrast-enhanced 3D T1-weighted black-blood and dedicated orbital contrast-enhanced T1-weighted Dixon sequences. There was no significant difference (P = .27) in the mean standardized contrast-to-noise ratio between contrast-enhanced T1-weighted black-blood (1.76 ± 1.07) and contrast-enhanced T1-weighted Dixon (2.29 ± 2.49) sequences. Contrast-enhanced 3D T1-weighted black-blood imaging is comparable in accuracy and qualitative/quantitative features with dedicated orbital contrast-enhanced T1-weighted Dixon imaging for the detection of acute optic neuritis. Therefore, when used, it has the potential to considerably shorten total patient imaging time.

Clinical utility of deep learning motion correction for T1 weighted MPRAGE MR images

PurposeTo evaluate the clinical utility of the application of a deep learning motion correction technique on 3D MPRAGE magnetic resonance images acquired in routine clinical practice. MethodsAn encoder-decoder deep learning network inspired by InceptionResnet was trained on public datasets. The clinical utility of the trained network was evaluated retrospectively on 27 3D MPRAGE T1 weighted motion degraded MR images identified by radiologists during reporting. The assessment of image quality was performed by one board-certified radiologist and one senior radiology trainee for nine neuroanatomical regions of the brain using a five-point visual grading scale. ResultsThe deep learning motion correction technique resulted in reduced ghosting, ringing and blurring for all the brain regions investigated. The larger regions of interest such as ventricles improved the least (1.81 to 1.16, p-value: < 0.0001) while the smaller but complex regions such as the hippocampus improved most (3.0 to 1.67, p-value: < 0.0001). The Wilcox rank tests of image quality differences for the nine neuroanatomical regions were all statistically significant (p < 0.001). Overall, 60 % of the neuroanatomical regions were improved, 39 % were unchanged and 1 % were degraded. Out of the unchanged cases, 28 % were already scored at the highest image quality before motion correction. It was found that approximately 13 % of repeated scans could be avoided using the DL motion correction approach. ConclusionThe deep learning motion correction technique improved the overall visual perception of the 3D T1 weighted MPRAGE brain images. This would improve the clinical utility of otherwise motion degraded images and allow visualisation of normal anatomy and even subtle pathology.

Hippocampal Dosimetry In Patients Receiving Radiosurgery For ≥ 25 Brain Metastases: Implications For HA-WBRT

Increasingly radiosurgery is used to manage patients with higher numbers of brain metastases in one or more sessions over time. For patients with ≥ 25 brain metastases who had radiosurgery (SRS) in single or multiple sessions, we report our dosimetric analysis of the hippocampi and the incidence of perihippocampal tumor location in this same cohort. From a review of our prospective registry, 47 patients treated with Gamma Knife SRS for ≥ 25 brain metastases between June 2013 and March 2019 were identified. Bilateral hippocampal contours were auto-generated on gadolinium-enhanced 3D MP-RAGE reference MRIs and manually edited per the RTOG hippocampus contouring atlas. Following RTOG 0933 guidelines, hippocampal avoidance regions (HA-region) were created by 5mm volumetric expansions. MRIs were co-registered with each SRS session in Gamma Plan, and the doses from each session were summed to calculate cumulative bilateral, left, and right hippocampal doses. Distribution of metastases relative to the HA-region was analyzed. The median number of cumulative tumors irradiated per patient was 38 (range 25-116) in a median of 3 (range 1-12) SRS sessions. The median cumulative tumor volume was 7.0 cc (range 0.8 to 27 cc), and the median marginal dose for the largest tumor per session was 16 Gy (10-21Gy). Of the total 1941 treated tumors, 55 (2.8%) were located in the HA-region, occurring in 31 of the 47 (66%) patients. Dosimetry is reported in Table 1. No patient experienced ≥ grade 3 neurologic toxicity. Large numbers of brain metastases can be treated by SRS with cumulative doses to the hippocampi which compare favorably to those reported with HA-WBRT and without adverse neurologic outcome. In addition, for patients with tumors located in the HA-regions and a high burden of intracranial disease, SRS affords hippocampal sparing. This is particularly relevant in light of our finding of eventual perihippocampal metastases in more than half our patients, a finding which precludes HA-WBRT, illustrating the importance of alternative hippocampus-sparing techniques such as SRS.Abstract 3704; TableAll PatientsNTIHATIHATIHA and >50 metastasesBilateral Hippocampus Mean (Gy)Median (Range)4.35 (1.71-12.26)3.03 (1.88-6.18)6.02 (1.71-12.26)9.48 (4.47-12.26)Bilateral Hippocampus D100 (Gy)Median (Range)1.75 (0.26-4.2)1.22 (0.54-3.47)2.03 (0.26-4.2)2.78 (2.15-4.2)Bilateral Hippocampus D40 (Gy)Median (Range)4.35 (1.52-10.29)2.97 (2.05-6.66)5.63 (1.52-10.29)8.97 (4.49-10.29)Bilateral Hippocampus Max (Gy)Median (Range)19.98 (3.29-63.24)7.09 (3.29-10.24)25.22 (11.11-63.24)35.34 (13.27-63.24)Left Hippocampus Mean (Gy)Median (Range)4.92 (1.20-14.30)3.44 (1.53-7.26)5.89 (1.20-14.30)10.03 (4.92-14.30)Abbreviations: NTIHA No Tumors in Hippocampal-Avoidance Region; TIHA Tumor(s) in Hippocampal-Avoidance Region Open table in a new tab

Simultaneous Diffusion and T1 Weighted Contrast Imaging for Human Brain Mapping

Introduction: Diffusion tensor imaging (DTI) is conventionally performed using echo planar imaging (EPI) for human brain mapping. However, EPI suffers from susceptibility distortion, requiring elaborate image post processing. Besides, DTI alone is limited in assessing gray and white matter boundaries of the brain, which is important for accurately imaging brain atrophy. The goal of this study was to design and evaluate simultaneous diffusion and T1 weighting high resolution imaging for human brain mapping. Materials and Methods: Three dimensional Magnetization-prepared rapid gradient-echo (3D MPRAGE) with T1 weighting, which is generally the method of choice for mapping gray and white matter structures in the brain, was extended to incorporate diffusion encoding using simulation and experiment to develop high resolution DTI and T1-weighted human brain data. Results: It is shown that the incorporation of DTI contrast (i.e. fractional anisotropy (FA) and mean diffusivity (MD)) into T1 weighted 3D MPRAGE using simulations as well as experimental results from in-vivo human brain studies at 4 Tesla magnetic field strength improves the contrast between gray and white matter sub-structural boundaries. Moreover, incorporating diffusion encoding into 3D MPRAGE avoids the inherent image distortions typically seen in EPI based DTI.Conclusion: This study suggests DTI weighted 3D MPRAGE combined with T1w is feasible for human brain imaging and expected to benefit improved assessment of gray/white matter boundaries.

Current Socioeconomic Status Correlates With Brain Volumes in Healthy Children and Adolescents but Not in Children With Prenatal Alcohol Exposure

Individuals with prenatal alcohol exposure (PAE) exhibit neurological deficits associated with brain injury including smaller brain volumes. Additional risk factors such as lower socioeconomic status (SES) may also have an impact on brain development for this population. This study examined how brain volumes are related to SES in both neurotypically developing children and adolescents, and those with PAE. 3D T1-weighted MPRAGE images were acquired from 69 participants with PAE (13.0 ± 3.2 years, range 7.1–18.8 years, 49% female) and 70 neurotypical controls (12.4 ± 2.9 years, range 7.0–18.5 years, 60% female) from four scanning sites in Canada. SES scores calculated using Hollingshead’s Four-Factor Index of Social Status from current caregiver placement were not significantly different between groups, though more children with PAE had lower SES scores compared to controls. Psychometric data comprised 14 cognitive measures, including executive functioning, attention and working memory, memory, math/numerical ability, and word reading. All cognitive scores were significantly worse in children with PAE compared to controls, though SES was not correlated with cognitive scores in either group after correction for multiple comparisons. All 13 brain volumes were smaller in children with PAE compared to children in the control group. Higher SES was associated with larger hippocampus and amygdala volumes in controls, but there were no such associations in children with PAE. Direct evaluation of the interaction between SES and diagnostic group did not show a significant differential impact of SES on these structures. These findings support previous links between SES and brain volumes in neurotypically developing children, but the lack of such a relationship with SES in children with PAE may be due to the markedly smaller brain volumes resulting from the initial brain injury and postpartum brain development, regardless of later SES.

Association between cortical volume and gray-white matter contrast with second generation antipsychotic medication exposure in first episode male schizophrenia patients

This cross-sectional study examines the differences in cortical volume and gray-to-white matter contrast (GWC) in first episode schizophrenia patients (SCZ) compared to healthy control participants (HC) and in SCZ patients as a function of exposure to second generation antipsychotic medication. We hypothesize 1) SCZ exhibit regionally lower cortical volumes relative to HCs, 2) cortical volume will be greater with longer exposure to second generation antipsychotics prior to the MRI scan, and 3) lower GWC with longer exposure to second generation antipsychotics prior to the MRI scan, suggesting more blurring from greater intracortical myelin. To accomplish this, MRI scans from 71 male SCZ patients treated with second generation oral risperidone and 42 male HCs were examined. 3D T1-weighted MPRAGE images collected at 1.5T were used to estimate cortical volume and GWC by sampling signal intensity at 30% within the cortical ribbon. Average cortical volume and GWC were calculated and compared between SCZ and HC. Cortical volume and GWC in SCZ patients were correlated with duration of medication exposure for the time period prior to the scan. First-episode SCZ patients had significantly lower cortical volume compared to HCs in bilateral temporal, superior and rostral frontal, postcentral gyral, and parahippocampal regions. In SCZ patients, greater cortical volume was associated with (log-transformed) duration of second-generation antipsychotic medication exposure in bilateral precuneus, right lingual, and right superior parietal regions. Lower GWC was correlated with longer duration of medication exposure bilaterally in the superior frontal lobes. In summary, second generation antipsychotics may increase cortical volume and decrease GWC in first episode SCZ patients.

Brain volume loss in individuals over time: Source of variance and limits of detectability

BackgroundBrain volume loss measured from magnetic resonance imaging (MRI) is a marker of neurodegeneration and predictor of disability progression in MS, and is commonly used to assess drug efficacy at the group level in clinical trials. Whether measures of brain volume loss could be useful to help guide management of individual patients depends on the relative magnitude of the changes over a given interval to physiological and technical sources of variability. GoalTo understand the relative contributions of neurodegeneration vs. physiological and technical sources of variability to measurements of brain volume loss in individuals. Material and methodsMultiple T1-weighted 3D MPRAGE images were acquired from a healthy volunteer and MS patient over varying time intervals: 7 times on the first day (before breakfast at 7:30AM and then every 2 ​h for 12 ​h), each day for the next 6 working days, and 6 times over the remainder of the year, on 2 ​Siemens MRI scanners: 1.5T Sonata (S1) and 3.0T TIM Trio (S2). Scan-reposition-rescan data were acquired on S2 for daily, monthly and 1-year visits. Percent brain volume change (PBVC) was measured from baseline to each follow-up scan using FSL/SIENA. We estimated the effect of physiologic fluctuations on brain volume using linear regression of the PBVC values over hourly and daily intervals. The magnitude of the physiological effect was estimated by comparing the root-mean-square error (RMSE) of the regression of all the data points relative to the regression line, for the hourly scans vs the daily scans. Variance due to technical sources was assessed as the RMSE of the regression over time using the intracranial volume as a reference. ResultsThe RMSE of PBVC over 12 ​h, for both scanners combined, (“Hours”, 0.15%), was similar to the day-to-day variation over 1 week (“Days”, 0.14%), and both were smaller than the RMS error over the year (0.21%). All of these variations, however, were smaller than the scan-reposition-rescan RMSE (0.32%). The variability of PBVC for the individual scanners followed the same trend. The standard error of the mean (SEM) for PBVC was 0.26 for S1, and 0.22 for S2. From these values, we computed the minimum detectable change (MDC) to be 0.7% on S1 and 0.6% on S2. The location of the brain along the z-axis of the magnet inversely correlated with brain volume change for hourly and daily brain volume fluctuations (p ​< ​0.01). ConclusionConsistent diurnal brain volume fluctuations attributable to physiological shifts were not detectable in this small study. Technical sources of variation dominate measured changes in brain volume in individuals until the volume loss exceeds around 0.6–0.7%. Reliable interpretation of measured brain volume changes as pathological (greater than normal aging) in individuals over 1 year requires changes in excess of about 1.1% (depending on the scanner). Reliable brain atrophy detection in an individual may be feasible if the rate of brain volume loss is large, or if the measurement interval is sufficiently long.

P1894Serum light-chain neurofilament is associated with brain atrophy in patients with atrial fibrillation

Abstract Background and aims There is emerging evidence that atrial fibrillation (AF) is associated with cognitive dysfunction, increased risk for dementia and reduced brain volume independent of stroke, but the underlying mechanisms of these associations remain unclear. Here, we investigated the association of serum light-chain neurofilament (sNfL), a neuroaxonal injury biomarker, with brain atrophy in AF patients. Methods Explorative analysis from the Swiss-AF cohort study, a multicenter prospective observationalstudy which recruited patients aged ≥45 years with documented AF (NCT02105844). In baseline blood samples, sNfL concentrations were measured in duplicates using a single-molecule array assay. Brain MRI was obtained at baseline and at two years using a standardized protocol including a 3D T1-weighted MPRAGE sequence, on which Structural Image Evaluation using Normalization of Atrophy (SIENA) with optimized parameters for brain extraction was applied to calculate the two-year percentage whole brain volume change (PBVC). Results We included 245 Swiss-AF patients (median age 73, 73% male). Two-year PBVC was significantly associated with baseline sNfL in linear regression, with a 0.09% whole brain volume decrease per 10 pg/ml sNfL increase (95% CI [0.05–0.13], p&lt;0.001). This association remained significant after adjustment for age, history of stroke and other vascular risk factors. Neurofilament and brain atrophy Conclusion Increasing baseline sNfL was predictive of higher two-year brain atrophy rates independent of stroke history in AF patients. This association might reflect a chronic neurodegenerative process in AF. Acknowledgement/Funding Swiss National Science Foundation

The impact of cervical spinal cord atrophy on quality of life in multiple sclerosis

BackgroundSpinal cord demyelination is common in multiple sclerosis (MS) and has been linked to increased disability and progressive clinical course. Spinal cord atrophy shows an especially close relationship to MS-related physical disability, though the relationship between spinal cord lesions/atrophy and health-related quality of life (QOL) has not been explored. Methods62 patients (53 relapsing MS, 7 secondary progressive, 2 clinically isolated syndrome) from our center underwent 3 T MRI within 30 days of clinical examination and QOL assessment. Upper cervical (C1-C3) spinal cord area (UCCA) was obtained from 3D high-resolution MPRAGE sequences (1 mm isotropic voxels). Cervical spinal cord (C1-C7) lesion count, and cervical and brain T2 hyperintense lesion volumes were calculated. Brain parenchymal fraction (BPF) was obtained from an automated segmentation pipeline. Spearman correlations were assessed between MRI and clinical data. Partial Spearman correlations adjusting for age, disease duration, and BPF assessed the independent association between MRI variables and QOL domains. ResultsUCCA showed an inverse relationship with age (r = −0.330, p = .009), disease duration, (r = −0.444, p < .001), and nine-hole peg test (r = −0.353, p = .005). The Upper Extremity Function QOL domain showed the strongest relationship to UCCA (r = 0.333, p = .008), with Lower Extremity Function QOL (r = 0.234, p = .067) and Satisfaction with Social Roles and Activities (r = 0.245, p = .055) correlations bordering significance. The association between UCCA and Upper Extremity QOL remained significant after adjustment for BPF, age, and disease duration. QOL domains reflective of psychological health (Depression, Anxiety, Emotional and Behavioral Dyscontrol, Positive Affect and Wellbeing) showed no relationship to UCCA. Cervical and brain lesion volume related to impairment in Stigma while cervical lesion count was unrelated to NeuroQOL impairment. Brain atrophy correlated with conventional markers of disability and cognition but did not have a significant relationship to QOL. ConclusionCervical spinal cord volume is independently associated with impaired upper extremity-related QOL in patients with MS. These findings suggest specific clinical relevance of MS-related spinal cord atrophy as compared to brain or cervical spinal cord lesions, or whole brain atrophy.

Response control correlates of anomalous basal ganglia morphology in boys, but not girls, with attention-deficit/hyperactivity disorder

Anomalous basal ganglia morphology may contribute to deficient motor response control in children with attention-deficit/hyperactivity disorder (ADHD). This study expands upon recent evidence of sex differences in subcortical morphology and motor response control deficits among children with ADHD to examine basal ganglia volume and shape in relation to motor response control. Participants included 8–12 year-old children with ADHD (n = 52, 21 girls) and typically developing (TD) controls (n = 45, 19 girls). High resolution T1-weighted 3D MPRAGE images covering the whole brain were acquired for all participants on a 3 T scanner. Participants performed two computer-based go/no-go tasks that differed in the extent to which working memory was necessary to guide response selection. Shape-based morphometric analyses were performed in addition to traditional volumetric comparisons and correlations with measures of motor response control were examined. Boys with ADHD consistently demonstrated increased commission error rate and response variability, regardless of task demands, suggesting broad response control deficits. In contrast, response control deficits among girls with ADHD varied depending on task demands and performance measures. Volumetric reductions and inward deformation (compression) on the dorsal surface of the globus pallidus and within subregions of the putamen receiving projections from limbic, executive and motor cortices were observed in boys, but not girls, with ADHD relative to TD children. Mediation analyses revealed that putamen and globus pallidus volumes mediated the relationship between diagnosis and commission error rate. Furthermore, reduced volumes of these structures and localized inward deformation within executive and motor circuits correlated with poorer response control, particularly under conditions of increased cognitive load. These findings suggest that anomalous basal ganglia morphology is related to impaired motor response control among boys with ADHD.

Thalamic and ventricular volumes predict motor response to deep brain stimulation for Parkinson's disease

BackgroundBrain atrophy frequently occurs with Parkinson's disease (PD) and relates to increased motor symptoms of PD. The predictive value of neuroimaging-based measures of global and regional brain volume on motor outcomes in deep brain stimulation (DBS) remains unclear but potentially could improve patient selection and targeting. ObjectivesTo determine the predictive value of preoperative volumetric MRI measures of cortical and subcortical brain volume on motor outcomes of subthalamic nucleus (STN) DBS in PD. MethodsPreoperative T1 3D MP-RAGE structural brain MRI images were analyzed for each participant to determine subcortical, ventricular, and cortical volume and thickness. Change in Unified Parkinson's Disease Rating Scale (UPDRS) scores for subsection 3, representing motor outcomes, was computed preoperatively and postoperatively following DBS programming in 86 participants. A multiple linear regression analysis was performed to investigate the relationship between volumetric data and the effect of DBS on UPDRS 3 scores. ResultsLarger ventricular and smaller thalamic volumes predicted significantly less improvement of UPDRS 3 scores after STN DBS. ConclusionsOur findings demonstrate in PD that regional brain volumes, in particular thalamic and ventricular volumes, predict motor outcomes after DBS. Differences in regional brain volumes may alter electrode targeting, reflect a specific disease trait such as postoperative progression of subclinical dementia, or directly interfere with the action of DBS.

Wave‐LORAKS: Combining wave encoding with structured low‐rank matrix modeling for more highly accelerated 3D imaging

Wave-CAIPI is a novel acquisition approach that enables highly accelerated 3D imaging. This paper investigates the combination of Wave-CAIPI with LORAKS-based reconstruction (Wave-LORAKS) to enable even further acceleration. LORAKS is a constrained image reconstruction framework that can impose spatial support, smooth phase, sparsity, and/or parallel imaging constraints. LORAKS requires minimal prior information, and instead uses the low-rank subspace structure of the raw data to automatically learn which constraints to impose and how to impose them. Previous LORAKS implementations addressed 2D image reconstruction problems. In this work, several recent advances in structured low-rank matrix recovery were combined to enable large-scale 3D Wave-LORAKS reconstruction with improved quality and computational efficiency. Wave-LORAKS was investigated by retrospective subsampling of two fully sampled Wave-encoded 3D MPRAGE datasets, and comparisons were made against existing Wave reconstruction approaches. Results show that Wave-LORAKS can yield higher reconstruction quality with 16×-accelerated data than is obtained by traditional Wave-CAIPI with 9×-accerated data. There are strong synergies between Wave encoding and LORAKS, which enables Wave-LORAKS to achieve higher acceleration and more flexible sampling compared to Wave-CAIPI.

Partial volume-aware assessment of multiple sclerosis lesions.

White-matter lesion count and volume estimation are key to the diagnosis and monitoring of multiple sclerosis (MS). Automated MS lesion segmentation methods that have been proposed in the past 20 years reach their limits when applied to patients in early disease stages characterized by low lesion load and small lesions. We propose an algorithm to automatically assess MS lesion load (number and volume) while taking into account the mixing of healthy and lesional tissue in the image voxels due to partial volume effects. The proposed method works on 3D MPRAGE and 3D FLAIR images as obtained from current routine MS clinical protocols. The method was evaluated and compared with manual segmentation on a cohort of 39 early-stage MS patients with low disability, and showed higher Dice similarity coefficients (median DSC = 0.55) and higher detection rate (median DR = 61%) than two widely used methods (median DSC = 0.50, median DR < 45%) for automated MS lesion segmentation. We argue that this is due to the higher performance in segmentation of small lesions, which are inherently prone to partial volume effects.

Cerebral structural characteristics in children with unilateral amblyopia: a MRI study

To study the mechanism of the development of amblyopia using the analysis of brain grey matter parameters. The areas primarily associated with visual cortex in children with amblyopia were analyzed. The study group comprised 8 right-handed children with left-sided amblyopia. MRI images were obtained by 1.5T Toshiba scanner with 3D MP-RAGE. T1-images were processed with FreeSurfer (5.3.0 version, http://surfer.nmr.mgh.harvard.edu/). No significant interhemisphere differences by cortical thickness were identified in all tested regions of interest. In correlation analysis, only the positive correlation between visual acuity in the left eye and cortical thickness in the left pericalcarine as well as the positive correlation between visual acuity in the left eye and cortical thickness in the left V1 area obtained using another anatomical atlas survived multiple comparison correction. The findings support the hypothesis that pathological ontogenetic processes in children with amblyopia lead to the structural abnormalities of the primary visual cortex.