Radiology - Research Publications

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    Stroke population-specific neuroanatomical CT-MRI brain atlas
    Kaffenberger, T ; Venkatraman, V ; Steward, C ; Thijs, VN ; Bernhardt, J ; Desmond, PM ; Campbell, BC ; Yassi, N (SPRINGER, 2022-01-30)
    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 ).
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    Assessment of the DTI-ALPS Parameter Along the Perivascular Space in Older Adults at Risk of Dementia
    Steward, CE ; Venkatraman, VK ; Lui, E ; Malpas, CB ; Ellis, KA ; Cyarto, EV ; Vivash, L ; O'Brien, TJ ; Velakoulis, D ; Ames, D ; Masters, CL ; Lautenschlager, NT ; Bammer, R ; Desmond, PM (WILEY, 2021-02-08)
    BACKGROUND AND PURPOSE: Recently, there has been growing interest in the glymphatic system (the functional waste clearance pathway for the central nervous system and its role in flushing solutes (such as amyloid ß and tau), metabolic, and other cellular waste products in the brain. Herein, we investigate a recent potential biomarker for glymphatic activity (the diffusion tensor imaging along the perivascular space [DTI-ALPS] parameter) using diffusion MRI imaging in an elderly cohort comprising 10 cognitively normal, 10 mild cognitive impairment (MCI), and 16 Alzheimer's disease (AD). METHODS: All 36 participants imaged on a Siemens 3.0T Tim Trio. Single-SE diffusion weighted Echo-planar imaging scans were acquired as well as T1 magnetization prepared rapid gradient echo, T2 axial, and susceptibility weighted imaging. Three millimeter regions of interest were drawn in the projection and association fibers adjacent to the medullary veins at the level of the lateral ventricle. The DTI-ALPS parameter was calculated in these regions and correlated with cognitive status, Mini-Mental State Examination (MMSE), and ADASCog11 measures. RESULTS: Significant correlations were found between DTI-ALPS and MMSE and ADASCog11 in the right hemisphere adjusting for age, sex, and APoE ε4 status. Significant differences were also found in the right DTI-ALPS indices between cognitively normal and AD groups (P < .026) and MCI groups (P < .025) in a univariate general linear model corrected for age, sex, and APoE ε4. Significant differences in apparent diffusion coefficient between cognitively normal and AD groups were found in the right projection fibers (P = .028). CONCLUSION: Further work is needed to determine the utility of DTI-ALPS index in larger elderly cohorts and whether it measures glymphatic activity.
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    Association between structural changes in brain with muscle function in sarcopenic older women: the women's healthy ageing project (WHAP)
    Hassan, EB ; Szoeke, C ; Vogrin, S ; Phu, S ; Venkatraman, V ; Desmond, P ; Steward, C ; Duque, G (JMNI, 2019-06-01)
    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.
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    Alterations in dorsal and ventral posterior cingulate connectivity in APOE epsilon 4 carriers at risk of Alzheimer's disease
    Kerestes, R ; Phal, PM ; Steward, C ; Moffat, BA ; Salinas, S ; Cox, KL ; Ellis, KA ; Cyarto, EV ; Ames, D ; Martins, RN ; Masters, CL ; Rowe, CC ; Sharman, MJ ; Salvado, O ; Szoeke, C ; Lai, M ; Lautenschlager, NT ; Desmond, PM (ROYAL COLL PSYCHIATRISTS, 2015-10-01)
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    Baseline White Matter Is Associated With Physical Fitness Change in Preclinical Alzheimer's Disease
    Venkatraman, VK ; Steward, CE ; Cox, KL ; Ellis, KA ; Phal, PM ; Sharman, MJ ; Villemagne, VL ; Lai, MMY ; Cyarto, E ; Ames, D ; Szoeke, C ; Rowe, CC ; Masters, CL ; Lautenschlager, NT ; Desmond, PM (FRONTIERS MEDIA SA, 2020-04-29)
    White matter (WM) microstructure is a sensitive marker to distinguish individuals at risk of Alzheimer's disease. The association of objective physical fitness (PF) measures and WM microstructure has not been explored and mixed results reported with physical activity (PA). Longitudinal studies of WM with PA and PF measures have had limited investigation. This study explored the relationship between objective PF measures over 24-months with "normal-appearing" WM microstructure. Data acquired on magnetic resonance imaging was used to measure "normal-appearing" WM microstructure at baseline and 24-months. Clinical variables such as cognitive and blood-based measures were collected longitudinally. Also, as part of the randomized controlled trial of a PA, extensive measures of PA and fitness were obtained over the 24 months. Bilateral corticospinal tracts (CST) and the corpus callosum showed a significant association between PF performance over 24-months and baseline WM microstructural measures. There was no significant longitudinal effect of the intervention or PF performance over 24-months. Baseline WM microstructural measures were significantly associated with PF performance over 24-months in this cohort of participants with vascular risk factors and at risk of Alzheimer's disease with distinctive patterns for each PF test.
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    Supranutritional Sodium Selenate Supplementation Delivers Selenium to the Central Nervous System: Results from a Randomized Controlled Pilot Trial in Alzheimer's Disease
    Cardoso, BR ; Roberts, BR ; Malpas, CB ; Vivash, L ; Genc, S ; Saling, MM ; Desmond, P ; Steward, C ; Hicks, RJ ; Callahan, J ; Brodtmann, A ; Collins, S ; Macfarlane, S ; Corcoran, NM ; Hovens, CM ; Velakoulis, D ; O'Brien, TJ ; Hare, DJ ; Bush, AI (SPRINGER, 2019-01-01)
    Insufficient supply of selenium to antioxidant enzymes in the brain may contribute to Alzheimer's disease (AD) pathophysiology; therefore, oral supplementation may potentially slow neurodegeneration. We examined selenium and selenoproteins in serum and cerebrospinal fluid (CSF) from a dual-dose 24-week randomized controlled trial of sodium selenate in AD patients, to assess tolerability, and efficacy of selenate in modulating selenium concentration in the central nervous system (CNS). A pilot study of 40 AD cases was randomized to placebo, nutritional (0.32 mg sodium selenate, 3 times daily), or supranutritional (10 mg, 3 times daily) groups. We measured total selenium, selenoproteins, and inorganic selenium levels, in serum and CSF, and compared against cognitive outcomes. Supranutritional selenium supplementation was well tolerated and yielded a significant (p < 0.001) but variable (95% CI = 13.4-24.8 μg/L) increase in CSF selenium, distributed across selenoproteins and inorganic species. Reclassifying subjects as either responsive or non-responsive based on elevation in CSF selenium concentrations revealed that responsive group did not deteriorate in Mini-Mental Status Examination (MMSE) as non-responsive group (p = 0.03). Pooled analysis of all samples revealed that CSF selenium could predict change in MMSE performance (Spearman's rho = 0.403; p = 0.023). High-dose sodium selenate supplementation is well tolerated and can modulate CNS selenium concentration, although individual variation in selenium metabolism must be considered to optimize potential benefits in AD. The Vel002 study is listed on the Australian and New Zealand Clinical Trials Registry ( http://www.anzctr.org.au /), ID: ACTRN12611001200976.
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    Tremor in multiple sclerosis is associated with cerebello-thalamic pathology
    Boonstra, F ; Florescu, G ; Evans, A ; Steward, C ; Mitchell, P ; Desmond, P ; Moffat, B ; Butzkueven, H ; Kolbe, S ; van der Walt, A (SPRINGER WIEN, 2017-12-01)
    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.
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    Assessment of Optic Pathway Structure and Function in Patients With Compression of the Optic Chiasm: A Correlation With Optical Coherence Tomography
    Phal, PM ; Steward, C ; Nichols, AD ; Kokkinos, C ; Desmond, PM ; Danesh-Meyer, H ; Sufaro, YZ ; Kaye, AH ; Moffat, BA (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2016-07-01)
    PURPOSE: The purpose of this study was to investigate correlations between retinal fiber thickness measured by optical coherence tomography (OCT) and anterograde functional and structural differences in the optic pathway of patients with compression of the optic chiasm. Our hypothesis was that loss of visual acuity caused by chronic compressive pathologies may lead to an irreversible decline in vision because of permanent neurodegeneration of the optic radiations and visual cortex. METHODS: Quantitative OCT, functional magnetic resonance imaging (MRI) and diffusion tensor MRI measurements were made in 17 patients being surgically treated for chiasmal compression. RESULTS: In our study we found that surgically irreversible visual field defects and reduced retinal nerve fiber layer thickness were significantly associated with lower fractional diffusion anisotropy and higher diffusivities in optic radiations and less functional MRI activation in the visual cortex. CONCLUSIONS: Damage to the retinal nerve fiber layer is associated with downstream structural and functional degradation of the optic pathway. This may be related to trans-synaptic degeneration and the fact that these factors are important potential imaging biomarkers for predicting visual recovery after surgical decompression.
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    Incidence of cerebral microbleeds in preclinical Alzheimer disease
    Yates, PA ; Desmond, PM ; Phal, PM ; Steward, C ; Szoeke, C ; Salvado, O ; Ellis, KA ; Martins, RN ; Masters, CL ; Ames, D ; Villemagne, VL ; Rowe, CC (LIPPINCOTT WILLIAMS & WILKINS, 2014-04-08)
    OBJECTIVE: We sought to determine the incidence and associations of lobar microbleeds (LMBs) in a longitudinal cohort with (11)C-Pittsburgh compound B (PiB) PET imaging. METHODS: One hundred seventy-four participants from the observational Australian Imaging, Biomarkers and Lifestyle Study of Ageing (97 with normal cognition [NC], 37 with mild cognitive impairment [MCI], and 40 with Alzheimer disease [AD] dementia) were assessed at 3 time points over 3 years with 3-tesla susceptibility-weighted MRI and (11)C-PiB PET. MRIs were inspected for microbleeds, siderosis, infarction, and white matter hyperintensity severity, blind to clinical and PiB findings. Neocortical PiB standardized uptake value ratio, normalized to cerebellar cortex, was dichotomized as positive or negative (PiB+/-, standardized uptake value ratio >1.5). Annualized LMB incidence was calculated, and logistic regression was used to determine the association of incident LMBs with PiB, APOE ε4+ status, and cerebrovascular disease. RESULTS: LMBs were present in 18.6% of NC, 24.3% of MCI, and 40% of AD participants (p < 0.05 vs NC). LMB incidence was 0.2 ± 0.6 per year in NC participants, 0.2 ± 0.5 in MCI, and 0.7 ± 1.4 in AD (p < 0.03 vs NC) and was 6-fold higher in PiB+ than PiB-NC. Incident LMBs were associated with age, APOE ε4+, PiB+, and baseline LMBs. Incidence of multiple LMBs was also associated with lacunar infarction and white matter hyperintensity severity. CONCLUSIONS: Older age, baseline LMBs, higher β-amyloid burden, and concomitant cerebrovascular disease may all confer higher risk of incident LMBs. This should be considered when designing protocols for amyloid-modifying clinical trials.