Radiology - Research Publications

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    Glutamate weighted imaging contrast in gliomas with 7 Tesla magnetic resonance imaging
    Neal, A ; Moffat, BA ; Stein, JM ; Nanga, RPR ; Desmond, P ; Shinohara, RT ; Hariharan, H ; Glarin, R ; Drummond, K ; Morokoff, A ; Kwan, P ; Reddy, R ; O'Brien, TJ ; Davis, KA (ELSEVIER SCI LTD, 2019)
    INTRODUCTION: Diffuse gliomas are incurable malignancies, which undergo inevitable progression and are associated with seizure in 50-90% of cases. Glutamate has the potential to be an important glioma biomarker of survival and local epileptogenicity if it can be accurately quantified noninvasively. METHODS: We applied the glutamate-weighted imaging method GluCEST (glutamate chemical exchange saturation transfer) and single voxel MRS (magnetic resonance spectroscopy) at 7 Telsa (7 T) to patients with gliomas. GluCEST contrast and MRS metabolite concentrations were quantified within the tumour region and peritumoural rim. Clinical variables of tumour aggressiveness (prior adjuvant therapy and previous radiological progression) and epilepsy (any prior seizures, seizure in last month and drug refractory epilepsy) were correlated with respective glutamate concentrations. Images were separated into post-hoc determined patterns and clinical variables were compared across patterns. RESULTS: Ten adult patients with a histo-molecular (n = 9) or radiological (n = 1) diagnosis of grade II-III diffuse glioma were recruited, 40.3 +/- 12.3 years. Increased tumour GluCEST contrast was associated with prior adjuvant therapy (p = .001), and increased peritumoural GluCEST contrast was associated with both recent seizures (p = .038) and drug refractory epilepsy (p = .029). We distinguished two unique GluCEST contrast patterns with distinct clinical and radiological features. MRS glutamate correlated with GluCEST contrast within the peritumoural voxel (R = 0.89, p = .003) and a positive trend existed in the tumour voxel (R = 0.65, p = .113). CONCLUSION: This study supports the role of glutamate in diffuse glioma biology. It further implicates elevated peritumoural glutamate in epileptogenesis and altered tumour glutamate homeostasis in glioma aggressiveness. Given the ability to non-invasively visualise and quantify glutamate, our findings raise the prospect of 7 T GluCEST selecting patients for individualised therapies directed at the glutamate pathway. Larger studies with prospective follow-up are required.
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    Audit of CT reporting standards in cases of intracerebral haemorrhage at a comprehensive stroke centre in Australia
    Barras, CD ; Asadi, H ; Phal, PM ; Tress, BM ; Davis, SM ; Desmond, PM (WILEY-BLACKWELL, 2016-12)
    INTRODUCTION: Multiple CT-derived biomarkers that are predictive of intracerebral haemorrhage (ICH) growth and outcome have been described in the literature, but the extent to which these appear in imaging reports of ICH is unknown. The aim of this retrospective process audit was to determine which of the known predictors of ICH outcome was recorded in reports of the disease, with a view to providing reporting recommendations, as appropriate. METHOD: We examined the initial CT report of patients diagnosed with ICH presenting to a metropolitan comprehensive stroke centre and meeting inclusion criteria during the audit period between 1 March 2013 and 28 February 2014. Each report was assessed for the inclusion of the following ICH characteristics: the number of measurement dimensions; volume; location; hydrocephalus; shape; density; 'CTA spot sign' (where CTA was performed). RESULTS: A total of 100 patients met audit inclusion criteria. At least one ICH dimension was recorded in 90% of reports; however, 39% did not include the measurements in three dimensions and volume was reported in just 6%. No ICH dimension was recorded in 10% of reports. With the exception of density and shape, reporting of other CT features exceeded 95%. Where CTA was performed (58%), 14 (24%) of 58 reported the 'CTA spot sign' status. CONCLUSION: In this audit, volume was the most under-reported of the established ICH characteristics predictive of ICH outcome. Readily calculated from multiplanar reformats using the ABC/2 technique, the routine reporting of ICH volume is recommended. More reporting attention to ICH density heterogeneity and shape irregularity is encouraged, given their emerging importance. Where acute CTA is performed, the presence of any dynamic haemorrhage (CTA spot sign) should be reported.
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    Emotional reactivity following surgery to the prefrontal cortex
    Jenkins, LM ; Andrewes, DG ; Nicholas, CL ; Drummond, KJ ; Moffat, BA ; Phal, PM ; Desmond, P (WILEY, 2018-03)
    We aimed to elicit emotion in patients with surgically circumscribed lesions of the prefrontal cortex (PFC) in order to elucidate the precise functional roles in emotion processing of the discrete subregions comprising the ventromedial PFC, including the medial PFC and orbitofrontal cortex (OFC). Three components of emotional reactivity were measured: subjective experience, behaviour, and physiological response. These included measures of self-reported emotion, observer-rated facial expression of emotion and measurements of heart rate and heart rate variability (HRV) during film viewing, and a measure of subjective emotional change since surgery. Patients with lesions to the ventromedial PFC demonstrated significant differences compared with controls in HRV during the film clips, suggesting a shift to greater dominance of sympathetic input. In contrast, patients with lesions restricted to the OFC showed significant differences in HRV suggesting reduced sympathetic input. They also showed less facial expression of emotion during positive film clips, and reported more subjective emotional change since surgery compared with controls. This human lesion study is important for refining theoretical models of emotion processing by the ventromedial PFC, which until now have primarily been based on anatomical connectivity, animal lesion, and human functional neuroimaging research. Such theories have implications for the treatment of a wide variety of emotional disorders.
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    Cerebrovascular disease, Alzheimer's disease biomarkers and longitudinal cognitive decline
    Yates, PA ; Villemagne, VL ; Ames, D ; Masters, CL ; Martins, RN ; Desmond, P ; Burnham, S ; Maruff, P ; Ellis, KA ; Rowe, CC (WILEY-BLACKWELL, 2016-06)
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    Clinical Integration of Automated Processing for Brain Quantitative Susceptibility Mapping: Multi-Site Reproducibility and Single-Site Robustness
    Spincemaille, P ; Liu, Z ; Zhang, S ; Kovanlikaya, I ; Ippoliti, M ; Makowski, M ; Watts, R ; de Rochefort, L ; Venkatraman, V ; Desmond, P ; Santin, MD ; Lehericy, S ; Kopell, BH ; Peran, P ; Wang, Y (WILEY, 2019-11)
    BACKGROUND AND PURPOSE: Quantitative susceptibility mapping (QSM) of the brain has become highly reproducible and has applications in an expanding array of diseases. To translate QSM from bench to bedside, it is important to automate its reconstruction immediately after data acquisition. In this work, a server system that automatically reconstructs QSM and exchange images with the scanner using the DICOM standard is demonstrated using a multi-site, multi-vendor reproducibility study and a large, single-site, multi-scanner image quality review study in a clinical environment. METHODS: A single healthy subject was scanned with a 3D multi-echo gradient echo sequence at nine sites around the world using scanners from three manufacturers. A high-resolution (HiRes, .5 × .5 × 1 mm3 reconstructed) and standard-resolution (StdRes, .5 × .5 × 3 mm3 ) protocol was performed. ROI analysis of various white matter and gray matter regions was performed to investigate reproducibility across sites. At one institution, a retrospective multi-scanner image quality review was carried out of all clinical QSM images acquired consecutively in 1 month. RESULTS: Reconstruction times using a GPU were 29 ± 22 seconds (StdRes) and 55 ± 39 seconds (HiRes). ROI standard deviation across sites was below 24 ppb (StdRes) and 17 ppb (HiRes). Correlations between ROI averages across sites were on average .92 (StdRes) and .96 (HiRes). Image quality review of 873 consecutive patients revealed diagnostic or excellent image quality in 96% of patients. CONCLUSION: Online QSM reconstruction for a variety of sites and scanner platforms with low cross-site ROI standard deviation is demonstrated. Image quality review revealed diagnostic or excellent image quality in 96% of 873 patients.
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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)
    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 ε4 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)
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    Ethical Issues in the Treatment of Late-Stage Alzheimer's Disease
    Watt, AD ; Jenkins, NL ; McColl, G ; Collins, S ; Desmond, PM (IOS PRESS, 2019)
    There is hope that the continuing efforts of researchers will yield a disease-modifying drug for Alzheimer's disease. Such a drug is likely to be capable of halting, or significantly slowing, the underlying pathological processes driving cognitive decline; however, it is unlikely to be capable of restoring brain function already lost through the pathological process. A therapy capable of halting Alzheimer's disease, while not providing restoration of function, may prompt serious ethical questions. For example, is there a stage in the disease process when it becomes too late for therapeutic intervention to commence? And who bears the responsibility of making such a decision? Conversations regarding the ethics of treating neurodegenerative conditions with non-restorative drugs have been largely absent within both clinical and research communities. Such discussions are urgently required to ensure that patients' rights and well-being are protected when such therapeutic options become available.
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    A Randomized Controlled Trial of Adherence to a 24-Month Home-Based Physical Activity Program and the Health Benefits for Older Adults at Risk of Alzheimer's Disease: The AIBL Active-Study
    Cox, KL ; Cyarto, E ; Ellis, KA ; Ames, D ; Desmond, P ; Phal, P ; Sharman, MJ ; Szoeke, C ; Rowe, CC ; Masters, CL ; You, E ; Burrows, S ; Lai, MMY ; Lautenschlager, NT ; Anstey, K ; Peters, R (IOS PRESS, 2019)
    BACKGROUND: Previous studies have demonstrated that physical activity (PA) interventions can improve physical and cognitive outcomes in older adults, but most have been relatively short in duration (<1 year) with a few having specifically targeting individuals at risk of developing Alzheimer's disease. OBJECTIVE: To examine adherence and physical health outcomes in a 24-month home-based PA intervention in older adults at risk of Alzheimer's disease. METHODS: Participants 60 years and older with mild cognitive impairment (MCI) or subjective memory complaints (SMC) with at least 1 cerebrovascular risk factor recruited from The Australian Imaging Biomarkers and Lifestyle Flagship Study of Aging (AIBL) were randomized to a PA or control group (n = 106). The control group continued with their usual lifestyle. The PA group received a 24-month home-based program with a target of 150 minutes/week of moderate PA and a behavioral intervention. Retention (participants remaining) and PA adherence (PA group only, percent PA completed to the PA prescribed) were determined at 6, 12, 18, and 24 months. Assessments at baseline, 6, 12, and 24 months included, PA; fitness; body composition and fat distribution. Key outcome measures were PA adherence and PA. RESULTS: The 24-month retention rate (97.2%) and the median PA adherence 91.67% (Q1-Q3, 81.96, 100.00) were excellent. In the long-term the intervention group achieved significantly better improvements in PA levels, leg strength, fat mass and fat distribution compared to the control. CONCLUSION: This study demonstrates that in this target group, long-term PA adherence is achievable and has physical health benefits.
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    Endovascular Thrombectomy for Ischemic Stroke Increases Disability-Free Survival, Quality of Life, and Life Expectancy and Reduces Cost
    Campbell, BCV ; Mitchell, PJ ; Churilov, L ; Keshtkaran, M ; Hong, K-S ; Kleinig, TJ ; Dewey, HM ; Yassi, N ; Yan, B ; Dowling, RJ ; Parsons, MW ; Wu, TY ; Brooks, M ; Simpson, MA ; Miteff, F ; Levi, CR ; Krause, M ; Harrington, TJ ; Faulder, KC ; Steinfort, BS ; Ang, T ; Scroop, R ; Barber, PA ; McGuinness, B ; Wijeratne, T ; Phan, TG ; Chong, W ; Chandra, RV ; Bladin, CF ; Rice, H ; de Villiers, L ; Ma, H ; Desmond, PM ; Meretoja, A ; Cadilhac, DA ; Donnan, GA ; Davis, SM (FRONTIERS MEDIA SA, 2017-12-14)
    BACKGROUND: Endovascular thrombectomy improves functional outcome in large vessel occlusion ischemic stroke. We examined disability, quality of life, survival and acute care costs in the EXTEND-IA trial, which used CT-perfusion imaging selection. METHODS: Large vessel ischemic stroke patients with favorable CT-perfusion were randomized to endovascular thrombectomy after alteplase versus alteplase-only. Clinical outcome was prospectively measured using 90-day modified Rankin scale (mRS). Individual patient expected survival and net difference in Disability/Quality-adjusted life years (DALY/QALY) up to 15 years from stroke were modeled using age, sex, 90-day mRS, and utility scores. Level of care within the first 90 days was prospectively measured and used to estimate procedure and inpatient care costs (US$ reference year 2014). RESULTS: There were 70 patients, 35 in each arm, mean age 69, median NIHSS 15 (IQR 12-19). The median (IQR) disability-weighted utility score at 90 days was 0.65 (0.00-0.91) in the alteplase-only versus 0.91 (0.65-1.00) in the endovascular group (p = 0.005). Modeled life expectancy was greater in the endovascular versus alteplase-only group (median 15.6 versus 11.2 years, p = 0.02). The endovascular thrombectomy group had fewer simulated DALYs lost over 15 years [median (IQR) 5.5 (3.2-8.7) versus 8.9 (4.7-13.8), p = 0.02] and more QALY gained [median (IQR) 9.3 (4.2-13.1) versus 4.9 (0.3-8.5), p = 0.03]. Endovascular patients spent less time in hospital [median (IQR) 5 (3-11) days versus 8 (5-14) days, p = 0.04] and rehabilitation [median (IQR) 0 (0-28) versus 27 (0-65) days, p = 0.03]. The estimated inpatient costs in the first 90 days were less in the thrombectomy group (average US$15,689 versus US$30,569, p = 0.008) offsetting the costs of interhospital transport and the thrombectomy procedure (average US$10,515). The average saving per patient treated with thrombectomy was US$4,365. CONCLUSION: Thrombectomy patients with large vessel occlusion and salvageable tissue on CT-perfusion had reduced length of stay and overall costs to 90 days. There was evidence of clinically relevant improvement in long-term survival and quality of life. CLINICAL TRIAL REGISTRATION: http://www.ClinicalTrials.gov NCT01492725 (registered 20/11/2011).