Developing High-Density Diffuse Optical Tomography for Neuroimaging

Clinicians who care for brain-injured patients and premature infants desire a bedside monitor of brain function. A decade ago, there was hope that optical imaging would be able to fill this role, as it combined fMRI\u27s ability to construct cortical maps with EEG\u27s portable, cap-based systems. However, early optical systems had poor imaging performance, and the momentum for the technique slowed. In our lab, we develop diffuse optical tomography: DOT), which is a more advanced method of performing optical imaging. My research has been to pioneer the in vivo use of DOT for advanced neuroimaging by: 1) quantifying the advantages of DOT through both in silico simulation and in vivo performance metrics,: 2) restoring confidence in the technique with the first retinotopic mapping of the visual cortex: a benchmark for fMRI and PET), and: 3) creating concepts and methods for the clinical translation of DOT. Hospitalized patients are unable to perform complicated neurological tasks, which has motivated us to develop the first DOT methods for resting-state brain mapping with functional connectivity. Finally, in collaboration with neonatologists, I have extended these methods with proof-of-principle imaging of brain-injured premature infants. This work establishes DOT\u27s improvements in imaging performance and readies it for multiple clinical and research roles

Multiscale imaging of the mouse cortex using two-photon microscopy and wide-field illumination

The mouse brain can be studied over vast spatial scales ranging from microscopic imaging of single neurons to macroscopic measurements of hemodynamics acquired over the majority of the mouse cortex. However, most neuroimaging modalities are limited by a fundamental trade-off between the spatial resolution and the field-of-view (FOV) over which the brain can be imaged, making it difficult to fully understand the functional and structural architecture of the healthy mouse brain and its disruption in disease. My dissertation has focused on developing multiscale optical systems capable of imaging the mouse brain at both microscopic and mesoscopic spatial scales, specifically addressing the difference in spatial scales imaged with two-photon microscopy (TPM) and optical intrinsic signal imaging (OISI). Central to this work has been the formulation of a principled design strategy for extending the FOV of the two-photon microscope. Using this design approach, we constructed a TPM system with subcellular resolution and a FOV area 100 times greater than a conventional two-photon microscope. To image the ellipsoidal shape of the mouse cortex, we also developed the microscope to image arbitrary surfaces within a single frame using an electrically tunable lens. Finally, to address the speed limitations of the TPM systems developed during my dissertation, I also conducted research in large-scale neural phenomena occurring in the mouse brain imaged with high-speed OISI. The work conducted during my dissertation addresses some of the fundamental principles in designing and applying optical systems for multiscale imaging of the mouse brain

Case series of breast fillers and how things may go wrong: radiology point of view

INTRODUCTION: Breast augmentation is a procedure opted by women to overcome sagging breast due to breastfeeding or aging as well as small breast size. Recent years have shown the emergence of a variety of injectable materials on market as breast fillers. These injectable breast fillers have swiftly gained popularity among women, considering the minimal invasiveness of the procedure, nullifying the need for terrifying surgery. Little do they know that the procedure may pose detrimental complications, while visualization of breast parenchyma infiltrated by these fillers is also deemed substandard; posing diagnostic challenges. We present a case series of three patients with prior history of hyaluronic acid and collagen breast injections. REPORT: The first patient is a 37-year-old lady who presented to casualty with worsening shortness of breath, non-productive cough, central chest pain; associated with fever and chills for 2-weeks duration. The second patient is a 34-year-old lady who complained of cough, fever and haemoptysis; associated with shortness of breath for 1-week duration. CT in these cases revealed non thrombotic wedge-shaped peripheral air-space densities. The third patient is a 37‐year‐old female with right breast pain, swelling and redness for 2- weeks duration. Previous collagen breast injection performed 1 year ago had impeded sonographic visualization of the breast parenchyma. MRI breasts showed multiple non- enhancing round and oval shaped lesions exhibiting fat intensity. CONCLUSION: Radiologists should be familiar with the potential risks and hazards as well as limitations of imaging posed by breast fillers such that MRI is required as problem-solving tool

Characterization of alar ligament on 3.0T MRI: a cross-sectional study in IIUM Medical Centre, Kuantan

INTRODUCTION: The main purpose of the study is to compare the normal anatomy of alar ligament on MRI between male and female. The specific objectives are to assess the prevalence of alar ligament visualized on MRI, to describe its characteristics in term of its course, shape and signal homogeneity and to find differences in alar ligament signal intensity between male and female. This study also aims to determine the association between the heights of respondents with alar ligament signal intensity and dimensions. MATERIALS & METHODS: 50 healthy volunteers were studied on 3.0T MR scanner Siemens Magnetom Spectra using 2-mm proton density, T2 and fat-suppression sequences. Alar ligament is depicted in 3 planes and the visualization and variability of the ligament courses, shapes and signal intensity characteristics were determined. The alar ligament dimensions were also measured. RESULTS: Alar ligament was best depicted in coronal plane, followed by sagittal and axial planes. The orientations were laterally ascending in most of the subjects (60%), predominantly oval in shaped (54%) and 67% showed inhomogenous signal. No significant difference of alar ligament signal intensity between male and female respondents. No significant association was found between the heights of the respondents with alar ligament signal intensity and dimensions. CONCLUSION: Employing a 3.0T MR scanner, the alar ligament is best portrayed on coronal plane, followed by sagittal and axial planes. However, tremendous variability of alar ligament as depicted in our data shows that caution needs to be exercised when evaluating alar ligament, especially during circumstances of injury

Protective microglial activation in Alzheimer’s disease pathogenesis

Here it was of interest to determine the spatiotemporal relationships between Aβ, tau, and microglial pathological changes in post-mortem human AD brains by comparing differentially affected brain regions. Immunohistochemistry and fluorescence immunohistochemistry targeting Aβ, tau, and the pan-microglia marker ionised calcium binding adaptor molecule 1 (Iba1) was performed in four regions of decreasing pathological severity: inferior temporal cortex, superior frontal cortex, primary visual cortex, and primary motor cortex of ten controls, five controls with Alzheimer changes (CAc), and eight AD cases. Following a validated modified disector sampling approach, using manual and corroborative automated methods, the results showed that activated microglia predominated in the inferior temporal cortex of CAc. AD brains were characterised by increased clustering of activated microglia in the primary visual cortex and a substantial loss of clustering and ramified healthy microglia in the inferior temporal cortex. Activated microglia were found to internalise Aβ pathology but not tau pathology. Further, microglia were found to phagocytose greater quantities of pre-synapses in AD compared to both CAc and controls in a study using super-resolution microscopy. Gene amplification studies of a number of candidate genes were performed in coronal neonatal mouse brain slice cultures treated with synthetic preparations of Aβ. Findings demonstrated the upregulation of select phagocytic and anti-inflammatory markers in response to low-dose Aβ monomers. Additionally, a validation amplification study confirmed findings from an RNA-Seq study which demonstrated the upregulation of gene transcripts related to immune pathways and phagocytosis in mildly affected regions of the AD brain. Taken together, these findings are indicative of neuroprotective activation of microglia early in the pathogenesis of AD