Fraser M. Callaghan

Bio: Fraser M. Callaghan is an academic researcher from The Heart Research Institute. The author has contributed to research in topics: Magnetic resonance imaging & Dissection (medical). The author has an hindex of 14, co-authored 25 publications receiving 456 citations. Previous affiliations of Fraser M. Callaghan include University of Sydney & ETH Zurich.

Revealing the Hippocampal Connectome through Super-Resolution 1150-Direction Diffusion MRI

Abstract: The hippocampus is a key component of emotional and memory circuits and is broadly connected throughout the brain. We tracked the whole-brain connections of white matter fibres from the hippocampus using ultra-high angular resolution diffusion MRI in both a single 1150-direction dataset and a large normal cohort (n = 94; 391-directions). Using a connectomic approach, we identified six dominant pathways in terms of strength, length and anatomy, and characterised them by their age and gender variation. The strongest individual connection was to the ipsilateral thalamus. There was a strong age dependence of hippocampal connectivity to medial occipital regions. Overall, our results concur with preclinical and ex-vivo data, confirming that meaningful in vivo characterisation of hippocampal connections is possible in an individual. Our findings extend the collective knowledge of hippocampal anatomy, highlighting the importance of the spinal-limbic pathway and the striking lack of hippocampal connectivity with motor and sensory cortices.

Use of multi-velocity encoding 4D flow MRI to improve quantification of flow patterns in the aorta

Abstract: Purpose To show that the use of a multi-velocity encoding (VENC) 4D-flow approach offers significant improvements in the characterization of complex flow in the aorta. Four-dimensional flow magnetic resonance imaging (MRI) (4D-flow) can be used to measure complex flow patterns and dynamics in the heart and major vessels. The quality of the information derived from these measures is dependent on the accuracy of the vector field, which is limited by the vector-to-noise ratio. Materials and Methods A 4D-flow protocol involving three different VENC values of 150, 60, and 20 cm/s was performed on six control subjects and nine patients with type-B chronic aortic dissection at 3T MRI. Data were processed using a single VENC value (150 cm/s) or using a fused dataset that selected the lowest appropriate VENC for each voxel. Performance was analyzed by measuring spatial vector angular correlation, magnitude correlation, temporal vector conservation, and “real-world” streamline tracing performance. Results The multi-VENC approach provided a 31% improvement in spatial and 53% improvement in temporal precision of velocity vector measurements during the mid-late diastolic period, where 99% of the flow vectors in the normal aorta are below 20 cm/s. In low-flow conditions this resulted in practical improvements of greater than 50% in pathline tracking and streamline tracing quantified by streamline curvature measurements. Conclusion A multi-VENC 4D-flow approach provides accurate vector data across normal physiological velocities observed in the aorta, dramatically improving outputs such as pathline tracking, streamline estimation, and further advanced analyses.J. Magn. Reson. Imaging 2015.

A disproportionate contribution of papillary muscles and trabeculations to total left ventricular mass makes choice of cardiovascular magnetic resonance analysis technique critical in Fabry disease

Abstract: Sphingolipid deposition in Fabry disease causes left ventricular (LV) hypertrophy, of which the accurate assessment is essential. Cardiovascular magnetic resonance (CMR) has been proposed as the gold standard. However, there is debate in the literature as to whether papillary muscles and trabeculations (P&T) should be included in LV mass (LVM). We examined the accuracy of 2 CMR methods of assessing LVM and LV volumes, including (M inc P&T) or excluding (M ex P&T) P&T, in a cohort of Fabry disease subjects (n = 20) compared to a matched control group (n = 20). Significant differences between the two measurement methods were observed for LV end-diastolic volume, LV end-systolic volume, LVM, and LV ejection fraction (LVEF) in both groups. These differences were significantly greater in the Fabry group compared to controls, except for LVEF. P&T contributed to a greater percentage of LVM in Fabry subjects than controls (20 ± 1% vs 13 ± 2%, p = 0.01). In the control group, both volume-derived methods (M inc P&T or MexP&T) provided accurate SV measurements compared with the internal reference of velocity-encoded aortic flow. In the Fabry group, inclusion of P&T (M inc P&T) resulted in good concordance with phase contrast flow imaging (difference between flow and volume techniques: 1 ± 3 ml, p = 0.7). The volumetric contribution of P&T in Fabry disease is markedly increased relative to healthy controls. Failure to account for this results in significant underestimation of LVM and results in misclassification of a proportion of subjects.

Cardiac involvement in genotype-positive Fabry disease patients assessed by cardiovascular MR

Abstract: Objective Cardiac magnetic resonance (CMR) has the potential to provide early detection of cardiac involvement in Fabry disease. We aimed to gain further insight into this by assessing a cohort of Fabry patients using CMR. Methods/results Fifty genotype-positive Fabry subjects (age 45±2 years; 50% male) referred for CMR and 39 matched controls (age 40±2 years; 59% male) were recruited. Patients had a mean Mainz severity score index of 15±2 (range 0–46), reflecting an overall mild degree of disease severity. Compared with controls, Fabry subjects had a 34% greater left ventricular mass (LVM) index (82±5 vs 61±2 g/m 2 , p=0.001) and had a significantly greater papillary muscle contribution to total LVM (13±1 vs 6±0.5%, p Conclusions CMR was able to detect cardiac involvement in 48% of this Fabry cohort, despite the overall mild disease phenotype of the cohort. Of those not on ERT, 21% were reclassified as having cardiac involvement allowing improved risk stratification and targeting of therapy.

Hydrodynamics of vegetated channels

Abstract: This paper highlights some recent trends in vegetation hydrodynamics, focusing on conditions within channels and spanning spatial scales from individual blades, to canopies or vegetation patches, to the channel reach. At the blade scale, the boundary layer formed on the plant surface plays a role in controlling nutrient uptake. Flow resistance and light availability are also influenced by the reconfiguration of flexible blades. At the canopy scale, there are two flow regimes. For sparse canopies, the flow resembles a rough boundary layer. For dense canopies, the flow resembles a mixing layer. At the reach scale, flow resistance is more closely connected to the patch-scale vegetation distribution, described by the blockage factor, than to the geometry of individual plants. The impact of vegetation distribution on sediment movement is discussed, with attention being paid to methods for estimating bed stress within regions of vegetation. The key research challenges of the hydrodynamics of vegetated channels ...

Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection.

Abstract: The potential for ischemic preconditioning to reduce infarct size was first recognized more than 30 years ago. Despite extension of the concept to ischemic postconditioning and remote ischemic conditioning and literally thousands of experimental studies in various species and models which identified a multitude of signaling steps, so far there is only a single and very recent study, which has unequivocally translated cardioprotection to improved clinical outcome as the primary endpoint in patients. Many potential reasons for this disappointing lack of clinical translation of cardioprotection have been proposed, including lack of rigor and reproducibility in preclinical studies, and poor design and conduct of clinical trials. There is, however, universal agreement that robust preclinical data are a mandatory prerequisite to initiate a meaningful clinical trial. In this context, it is disconcerting that the CAESAR consortium (Consortium for preclinicAl assESsment of cARdioprotective therapies) in a highly standardized multi-center approach of preclinical studies identified only ischemic preconditioning, but not nitrite or sildenafil, when given as adjunct to reperfusion, to reduce infarct size. However, ischemic preconditioning—due to its very nature—can only be used in elective interventions, and not in acute myocardial infarction. Therefore, better strategies to identify robust and reproducible strategies of cardioprotection, which can subsequently be tested in clinical trials must be developed. We refer to the recent guidelines for experimental models of myocardial ischemia and infarction, and aim to provide now practical guidelines to ensure rigor and reproducibility in preclinical and clinical studies on cardioprotection. In line with the above guideline, we define rigor as standardized state-of-the-art design, conduct and reporting of a study, which is then a prerequisite for reproducibility, i.e. replication of results by another laboratory when performing exactly the same experiment.

A prospectus for periphyton: recent and future ecological research

Abstract: The presence, abundance, composition, and growth of periphyton are controlled or influenced by 5 broad classes of environmental variation: disturbances, stressors, resources, hydraulic conditions, and biotic interactions. In turn, periphyton communities affect water chemistry, hydraulic conditions, habitat availability, and foodweb dynamics. This review focuses on responses of periphyton communities to environmental variation. A specific objective of the review is to identify robust periphyton–environment relationships and insightful concepts. Contributors to J-NABS have led the field in testing and expanding concepts in periphyton ecology. J-NABS papers about periphyton patch dynamics, light- and nutrient-limited periphyton growth, and the effects of disturbances on periphyton structure and function have been particularly influential. However, many topics in periphyton ecology remain unexplored and underexplored. These topics include resource colimitation, physiological responses to stressors, al...

The fundamental role of ecological feedback mechanisms for the adaptive management of seagrass ecosystems - a review.

Abstract: Seagrass meadows are vital ecosystems in coastal zones worldwide, but are also under global threat. One of the major hurdles restricting the success of seagrass conservation and restoration is our limited understanding of ecological feedback mechanisms. In these ecosystems, multiple, self-reinforcing feedbacks can undermine conservation efforts by masking environmental impacts until the decline is precipitous, or alternatively they can inhibit seagrass recovery in spite of restoration efforts. However, no clear framework yet exists for identifying or dealing with feedbacks to improve the management of seagrass ecosystems. Here we review the causes and consequences of multiple feedbacks between seagrass and biotic and/or abiotic processes. We demonstrate how feedbacks have the potential to impose or reinforce regimes of either seagrass dominance or unvegetated substrate, and how the strength and importance of these feedbacks vary across environmental gradients. Although a myriad of feedbacks have now been identified, the co-occurrence and likely interaction among feedbacks has largely been overlooked to date due to difficulties in analysis and detection. Here we take a fundamental step forward by modelling the interactions among two distinct above- and belowground feedbacks to demonstrate that interacting feedbacks are likely to be important for ecosystem resilience. On this basis, we propose a five-step adaptive management plan to address feedback dynamics for effective conservation and restoration strategies. The management plan provides guidance to aid in the identification and prioritisation of likely feedbacks in different seagrass ecosystems.