Stroke population-specific neuroanatomical CT-MRI brain atlas.

PURPOSE: Development of a freely available stroke population-specific anatomical CT/MRI atlas with a reliable normalisation pipeline for clinical CT. METHODS: By reviewing CT scans in suspected stroke patients and filtering the AIBL MRI database, respectively, we collected 50 normal-for-age CT and MRI scans to build a standard-resolution CT template and a high-resolution MRI template. The latter was manually segmented into anatomical brain regions. We then developed and validated a MRI to CT registration pipeline to align the MRI atlas onto the CT template. Finally, we developed a CT-to-CT-normalisation pipeline and tested its reliability by calculating Dice coefficient (Dice) and Average Hausdorff Distance (AHD) for predefined areas in 100 CT scans from ischaemic stroke patients. RESULTS: The resulting CT/MRI templates were age and sex matched to a general stroke population (median age 71.9 years (62.1-80.2), 60% male). Specifically, this accounts for relevant structural changes related to aging, which may affect registration. Applying the validated MRI to CT alignment (Dice > 0.78, Average Hausdorff Distance < 0.59 mm) resulted in our final CT-MRI atlas. The atlas has 52 manually segmented regions and covers the whole brain. The alignment of four cortical and subcortical brain regions with our CT-normalisation pipeline was reliable for small/medium/large infarct lesions (Dice coefficient > 0.5). CONCLUSION: The newly created CT-MRI brain atlas has the potential to standardise stroke lesion segmentation. Together with the automated normalisation pipeline, it allows analysis of existing and new datasets to improve prediction tools for stroke patients (free download at https://forms.office.com/r/v4t3sWfbKs ).

The impact of hippocampal segmentation methods on correlations with clinical data.

BACKGROUND: In vivo measurement of hippocampal volume with magnetic resonance imaging (MRI) has become an important element in neuroimaging research. However, hippocampal volumetric findings and their relationship with cardiovascular risk factors and memory performance are still controversial and inconsistent for non-demented adults. PURPOSE: To compare total and regional hippocampal volumes from manual tracing and automated Freesurfer segmentation methods and their relationship with mid-life clinical data and late-life verbal episodic memory performance in older women. MATERIAL AND METHODS: This study used structural MRI datasets from 161 women who were scanned in 2012 and underwent neuropsychological assessments. Of these participants, 135 women had completed baseline measures of cardiovascular risk factors in 1992. RESULTS: Our results showed a significant correlation between manual tracing and automated Freesurfer output segmentations of total (r = 0.71), anterior (r = 0.65), and posterior (r = 0.38) hippocampal volumes. Mid-life Framingham Cardiovascular Risk Profile score is not associated with late-life hippocampal volumes, adjusted for intracranial volume, age, education, and apolipoprotein E gene ε4 status. Anterior hippocampal volume segmented either with manual tracing or automated Freesurfer software is sensitive to changes in mid-life high-density lipoprotein (HDL) cholesterol level, while posterior hippocampal volume is linked with verbal episodic memory performance in elderly women. CONCLUSION: These findings support the use of Freesurfer automated segmentation measures for large datasets as being highly correlated with the manual tracing method. In addition, our results suggest intervention strategies that target mid-life HDL cholesterol level in women.

Association between structural changes in brain with muscle function in sarcopenic older women: the women's healthy ageing project (WHAP).

OBJECTIVES: The involvement of changes in brain structure in the pathophysiology of muscle loss (sarcopenia) with aging remains unclear. In this study, we investigated the associations between brain structure and muscle strength in a group of older women. We hypothesized that structural changes in brain could correlate with functional changes observed in sarcopenic older women. METHODS: In 150 women (median age of 70 years) of the Women's Healthy Ageing Project (WHAP) Study, brain grey (total and cortex) volumes were calculated using magnetic resonance imaging (MRI) analyses. Grip strength and timed up and go (TUG) were measured. The brain volumes were compared between sarcopenic vs. non-sarcopenic subjects and women with previous falls vs. those without. RESULTS: Based on handgrip strength and TUG results respectively, 27% and 15% of women were classified as sarcopenic; and only 5% were sarcopenic based on both criteria. At least one fall was experienced by 15% of participants. There was no difference in brain volumetric data between those with vs. without sarcopenia (p>0.24) or between women with falls (as a symptom of weakness or imbalance) vs. those without history of falls (p>0.25). CONCLUSIONS: Brain structure was not associated with functional changes or falls in this population of older women.

Tremor in multiple sclerosis is associated with cerebello-thalamic pathology.

Tremor in people with multiple sclerosis (MS) is a frequent and debilitating symptom with a relatively poorly understood pathophysiology. To determine the relationship between clinical tremor severity and structural magnetic resonance imaging parameters. Eleven patients with clinically definite MS and right-sided upper limb tremor were studied. Tremor severity was assessed using the Bain score (overall severity, writing, and Archimedes spiral drawing). Cerebellar dysfunction was assessed using the Scale for the Assessment and Rating of Ataxia. Dystonia was assessed using the Global Dystonia Scale adapted for upper limb. For all subjects, volume was calculated for the thalamus from T1-weighted volumetric scans using Freesurfer. Superior cerebellar peduncle (SCP) cross-sectional areas were measured manually. The presence of lesions was visually determined and the lesion volumes were calculated by the lesion growth algorithm as implemented in the Lesion Segmentation Toolbox. Right thalamic volume negatively correlated with Bain tremor severity score (ρ = - 0.65, p = 0.03). Left thalamic volume negatively correlated with general Bain tremor severity score (ρ = - 0.65, p = 0.03) and the Bain writing score (ρ = - 0.65, p = 0.03). Right SCP area negatively correlated with Bain writing score (ρ = - 0.69, p = 0.02). Finally, Bain Archimedes score was significantly higher in patients with lesions in the contralateral thalamus. Whole brain lesion load showed no relationship with tremor severity. These results implicate degeneration of key structures within the cerebello-thalamic pathway as pathological substrates for tremor in MS patients.

Early childhood trauma and hippocampal volumes in patients with epileptic and psychogenic seizures.

OBJECTIVE: Exposure to early life childhood trauma has been implicated as resulting in a vulnerability to epileptic and psychogenic nonepileptic seizures (PNES), hippocampal atrophy, and psychiatric disorders. This study aimed to explore the relationships between childhood trauma, epilepsy, PNES, and hippocampal volume in patients admitted to a video-electroencephalogram monitoring (VEM) unit. METHODS: One hundred thirty-one patients were recruited from the Royal Melbourne Hospital VEM unit. The diagnostic breakdown of this group was: temporal lobe epilepsy (TLE) (32), other epilepsy syndromes (35), PNES (47), other nonepileptic syndromes (5), both epilepsy and PNES (6), and uncertain diagnosis (6). All patients completed a questionnaire assessing exposure to childhood trauma, the Childhood Trauma Questionnaire (CTQ), as well as questionnaires assessing psychiatric symptomatology (SCL-90-R), Anxiety and Depression (HADS), quality of life (QOLIE-98) and cognition (NUCOG). Volumetric coronal T1 MRI scans were available for 84 patients. Hippocampal volumes were manually traced by a blinded operator. RESULTS: The prevalence of childhood trauma in patients with PNES was higher than in patients with other diagnoses (p=0.005), and the group with PNES overall scored significantly higher on the CTQ (p=0.002). No association was found between CTQ scores and hippocampal volumes; however, patients with a history of sexual abuse were found to have smaller left hippocampal volumes than patients who had not (p=0.043). Patients reporting having experienced childhood trauma scored lower on measures of quality of life and higher on measures of psychiatric symptomatology. SIGNIFICANCE: Patients with PNES report having experienced significantly more childhood trauma than those with epileptic seizures, and in both groups there was a relationship between a history of having experienced sexual abuse and reduced left hippocampal volume. Patients with PNES and those with epilepsy who have a history of childhood trauma have overall worse quality of life and more psychiatric symptomatology.

Effects of a physical activity intervention on brain atrophy in older adults at risk of dementia: a randomized controlled trial.

Lack of physical activity is a risk factor for dementia, however, the utility of interventional physical activity programs as a protective measure against brain atrophy and cognitive decline is uncertain. Here we present the effect of a randomized controlled trial of a 24-month physical activity intervention on global and regional brain atrophy as characterized by longitudinal voxel-based morphometry with T1-weighted MRI images. The study sample consisted of 98 participants at risk of dementia, with mild cognitive impairment or subjective memory complaints, and having at least one vascular risk factor for dementia, randomized into an exercise group and a control group. Between 0 and 24 months, there was no significant difference detected between groups in the rate of change in global, or regional brain volumes.

The effect of midlife cardiovascular risk factors on white matter hyperintensity volume and cognition two decades later in normal ageing women.

Cerebral White Matter Hyperintensity (WMH) lesions have been identified as markers of cerebrovascular diseases and they are associated with increased risk of cognitive impairment. In this study, we investigated the relationship between midlife cardiovascular risk factors and late life WMH volumes two decades later, and examined their association with cognitive performance. 135 participants from the Women's Healthy Ageing Project had completed midlife cardiovascular risk measurement in 1992 and late life brain MRI scan and cognitive assessment in 2012. In these community-dwelling normal aging women, we found that higher midlife Framingham Cardiovascular Risk Profile (FCRP) score was associated with greater WMH volume two decades later, and was predominantly driven by the impact of HDL cholesterol level, controlling for age, education and APOE ε4 status. Structural equation modelling demonstrated that the relationship between midlife FCRP score and late life executive function was mediated by WMH volume. These findings suggest intervention strategies that target major cardiovascular risk factors at midlife might be effective in reducing the development of WMH lesions and thus late life cognitive decline.

A decade of changes in brain volume and cognition.

Brain atrophy can occur several decades prior to onset of cognitive impairments. However, few longitudinal studies have examined the relationship between brain volume changes and cognition over a long follow-up period in healthy elderly women. In the present study we investigate the relationship between whole brain and hippocampal atrophy rates and longitudinal changes in cognition, including verbal episodic memory and executive function, in older women. We also examine whether baseline brain volume predicts subsequent changes in cognitive performance over a 10-year period. A total of 60 individuals from the population-based Women's Healthy Ageing Project with a mean age at baseline of 59 years underwent 3T MRI. Of these, 40 women completed follow-up cognitive assessments, 23 of whom had follow-up MRI scans. Linear regression analysis was used to examine the relationship between brain atrophy and changes in verbal episodic memory and executive function over a 10-year period. The results show that baseline measurements of frontal and temporal grey matter volumes predict changes in verbal episodic memory performance, whereas hippocampal volume at baseline is associated with changes in executive function performance over a 10-year period of follow-ups. In addition, higher whole brain and hippocampal atrophy rates are correlated with a decline in verbal episodic memory. These findings indicate that in addition to atrophy rate, smaller regional grey matter volumes even 10 years prior is associated with increased rates of cognitive decline. This study suggests useful neuroimaging biomarkers for the prediction of cognitive decline in healthy elderly women.

An ovine model of cerebral catheter venography for implantation of an endovascular neural interface.

OBJECTIVE Neural interface technology may enable the development of novel therapies to treat neurological conditions, including motor prostheses for spinal cord injury. Intracranial neural interfaces currently require a craniotomy to achieve implantation and may result in chronic tissue inflammation. Novel approaches are required that achieve less invasive implantation methods while maintaining high spatial resolution. An endovascular stent electrode array avoids direct brain trauma and is able to record electrocorticography in local cortical tissue from within the venous vasculature. The motor area in sheep runs in a parasagittal plane immediately adjacent to the superior sagittal sinus (SSS). The authors aimed to develop a sheep model of cerebral venography that would enable validation of an endovascular neural interface. METHODS Cerebral catheter venography was performed in 39 consecutive sheep. Contrast-enhanced MRI of the brain was performed on 13 animals. Multiple telescoping coaxial catheter systems were assessed to determine the largest wide-bore delivery catheter that could be delivered into the anterior SSS. Measurements of SSS diameter and distance from the motor area were taken. The location of the motor area was determined in relation to lateral and superior projections of digital subtraction venography images and confirmed on MRI. RESULTS The venous pathway from the common jugular vein (7.4 mm) to the anterior SSS (1.2 mm) was technically challenging to selectively catheterize. The SSS coursed immediately adjacent to the motor cortex (< 1 mm) for a length of 40 mm, or the anterior half of the SSS. Attempted access with 5-Fr and 6-Fr delivery catheters was associated with longer procedure times and higher complication rates. A 4-Fr catheter (internal lumen diameter 1.1 mm) was successful in accessing the SSS in 100% of cases with no associated complications. Complications included procedure-related venous dissection in two major areas: the torcular herophili, and the anterior formation of the SSS. The bifurcation of the cruciate sulcal veins with the SSS was a reliable predictor of the commencement of the motor area. CONCLUSIONS The ovine model for cerebral catheter venography has generalizability to the human cerebral venous system in relation to motor cortex location. This novel model may facilitate the development of the novel field of endovascular neural interfaces that may include preclinical investigations for cortical recording applications such as paralysis and epilepsy, as well as other potential applications in neuromodulation.

Alterations in dorsal and ventral posterior cingulate connectivity in APOE ε4 carriers at risk of Alzheimer's disease.

BACKGROUND: Recent evidence suggests that exercise plays a role in cognition and that the posterior cingulate cortex (PCC) can be divided into dorsal and ventral subregions based on distinct connectivity patterns. AIMS: To examine the effect of physical activity and division of the PCC on brain functional connectivity measures in subjective memory complainers (SMC) carrying the epsilon 4 allele of apolipoprotein E (APOE ε4) allele. METHOD: Participants were 22 SMC carrying the APOE ε4 allele (ε4+; mean age 72.18 years) and 58 SMC non-carriers (ε4-; mean age 72.79 years). Connectivity of four dorsal and ventral seeds was examined. Relationships between PCC connectivity and physical activity measures were explored. RESULTS: ε4+ individuals showed increased connectivity between the dorsal PCC and dorsolateral prefrontal cortex, and the ventral PCC and supplementary motor area (SMA). Greater levels of physical activity correlated with the magnitude of ventral PCC-SMA connectivity. CONCLUSIONS: The results provide the first evidence that ε4+ individuals at increased risk of cognitive decline show distinct alterations in dorsal and ventral PCC functional connectivity. DECLARATION OF INTEREST: D.A. has served on scientific advisory boards for Novartis, Eli Lilly, Janssen, Prana and Pfizer, and as Editor-in-Chief for International Psychogeriatrics; received speaker honoraria from Pfizer and Lundbeck, and research support from Eli Lilly, GlaxoSmithKline, Forest Laboratories, Novartis, and CSIRO. C.L.M. has received consulting fees from Eli Lilly and Prana Biotechnology, and has stock ownership in Prana Biotechnology. C.C.R. has received consultancy payments from Roche and Piramal, and research support from Avid Radiopharmaceuticals, Eli Lilly, GE Healthcare, Piramal and Navidea for amyloid imaging. C.S. has provided clinical consultancy and been on scientific advisory committees for the Australian CSIRO, Alzheimer's Australia, University of Melbourne and other relationships, which are subject to confidentiality clauses; she has been a named Chief Investigator on investigator-driven collaborative research projects in partnership with Pfizer, Merck, Piramal, Bayer and GE Healthcare. Her research programme has received support from the National Health and Medical Research Council Alzheimer's Association, Collier Trust, Scobie and Claire McKinnon Foundation, JO and JR Wicking Trust, Shepherd Foundation, Brain Foundation, Mason Foundation, Ramaciotti Foundation, Alzheimer's Australia and the Royal Australian College of Physicians. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.