BIRDS

J King, E Gibbons, C Graham, J Walsh, Geneva: Picker Institute Europe and University of Oxford, 2013 - Cited by 17

JP Henderson, JJ Walsh, Topology and its Applications, 1983 - Cited by 15

JJ Walsh, BV Lewis, BJOG: An International Journal of Obstetrics & Gynaecology, 1970 - Cited by 15

JE Walsh, Physical Review Letters, 1971 - Cited by 14

D Coman, DC Peters, JJ Walsh, LJ Savic, S Huber, AJ Sinusas, MD Lin, J Chapiro, RT Constable, DL Rothman…, Magnetic resonance in medicine, 2020 - Cited by 14

CA Young, J Ealing, C McDermott, T Williams, A Al-Chalabi, T Majeed, G Burke, A Pinto, D Dick, K Talbot…, Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2019 - Cited by 17

Since brain’s microvasculature is compromised in gliomas, intravenous injection of tumor-targeting nanoparticles containing drugs (D-NPs) and superparamagnetic iron oxide (SPIO-NPs) can deliver high payloads of drugs while allowing MRI to track drug distribution. However, therapeutic effect of D-NPs remains poorly investigated because superparamagnetic fields generated by SPIO-NPs perturb conventional MRI readouts. Because extracellular pH () is a tumor hallmark, mapping is critical. Brain is measured by biosensor imaging of redundant deviation in shifts (BIRDS) with lanthanide agents, by detecting paramagnetically shifted resonances of nonexchangeable protons on the agent. To test the hypothesis that BIRDS-based readout remains uncompromised by presence of SPIO-NPs, we mapped in glioma-bearing rats before and after SPIO-NPs infusion. While SPIO-NPs accumulation in the tumor enhanced MRI contrast, the inside and outside the MRI-defined tumor boundary remained unchanged after SPIO-NPs infusion, regardless of the tumor type (9L versus RG2) or agent injection method (renal ligation versus coinfusion with probenecid). These results demonstrate that we can simultaneously and noninvasively image the specific location and the healing efficacy of D-NPs, where MRI contrast from SPIO-NPs can track their distribution and BIRDS-based can map their therapeutic impact.

This thesis presents sodium magnetic resonance as an in vivo means for non-invasively visualizing the changes in cell sodium ion homeostasis that occur in ischemic tissue during acute stroke. Single quantum sodium magnetic resonance imaging (MRI) was used to determine the time course of tissue sodium concentration (TSC) in a non-human primate model of reversible focal brain ischemia. In each animal, TSC increased slowly and linearly as a function of time after the onset of focal brain ischemia. Changes in the TSC accumulation were seen upon reperfusion. The results demonstrate that the increase in TSC in ischemic tissue is readily measurable using sodium MRI at clinical magnetic field strengths (3.0 T) in acceptable imaging times (5 minutes). The results also indicate that sodium MRI could predict the stroke onset time in patients that are unsure when their symptoms began, potentially extending the use of thrombolytic therapy to patients that would otherwise not receive treatment. Many studies have hypothesized that the best means for the in vivo study of the changes in cell sodium ion homeostasis that occur during brain ischemia is to use imaging schemes that isolate the sodium NMR signal from the intracellular compartment. This thesis investigates the contribution of the extracellular sodium pool to the brain's triple quantum (TQ) sodium MR signal in the rat using the thulium shift reagent, TmDOTP5-. Within the SNR of the experiment, there was no evidence of any contribution to the TQ sodium MR signal from the sodium in the extracellular brain, vascular, and muscle spaces in the head. Finally, TQ sodium MR images in the in vivo non-human primate are presented for the first time. Moreover, these images were obtained in clinically acceptable 18 minute data acquisition times. TQ sodium MRI during non-human primate focal brain ischemia identified large changes in the ischemic region as early as 34 minutes after the onset of ischemia. The increase in the TQ sodium MRI signal intensity observed in the ischemic hemisphere is hypothesized to be due to an increase in the intracellular sodium concentration as a result of impaired ion homeostasis during evolving brain ischemia.

Magnetic Resonance Imaging (MRI) is a popular imaging modality due to its ability to provide excellent soft tissue contrast without exposure to ionizing radiation. It can be used for temperature monitoring (thermometry) as well as for assessing the biochemistry in vivo (MRS). This dissertation focuses separately on the development, application and quantitation issues of these two aspects of MRI. Radiofrequency (RF)-induced tissue heating is a concern in MRI. The dosimetric quantity for monitoring RF heating is the Specific Absorption Rate (SAR) defined as the RF power absorbed per unit mass of tissue. A novel approach for imaging SAR from absolute temperature images obtained using a paramagnetic lanthanide complex-Thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis (methylene phosphonate) (TmDOTP5-) was developed. The effects of a bare-ended, insulated conductor in a phantom were investigated by 3D SAR imaging. 3D SAR maps were also generated using a high SAR sequence while varying the pulse duration. The high spatial resolution SAR maps correctly identified the local SAR rise near the wire end and also revealed increasing SAR with increasing pulse duration in the high SAR sequence, as expected. These results demonstrate the potential of MR thermometry with paramagnetic lanthanide complexes for evaluating safety of implants, medical devices as well as different pulse sequences. The second part of the thesis is dedicated to the technique of measuring in vivo levels of the neurotransmitter γ-aminobutyric acid (GABA) using MRS. GABA is an inhibitory neurotransmitter in the brain which is involved in the control of fine movement and balance. GABA MRS with spectral editing was performed and GABA was quantified using custom fitting parameters in the tool LCModel to measure changes in movement disorders - particularly Parkinson's disease (PD) and sleep bruxism. Higher levels of thalamic GABA were detected in PD with correlation to disease severity indicating the possibility to use GABA MRS as a biomarker for PD progression. On the other hand, in the bruxers, lower levels of GABA correlating with higher levels of glutamate in the dorso-lateral prefrontal cortex were detected indicating disturbances in the GABAergic and glutamatergic pathways. Lastly, since GABA quantification is a much discussed topic in literature with no one, clear and best approach, an effort was made to compare some popular fitting approaches in LCModel. Semi-synthetic simulated GABA spectra were used to test the accuracy, sensitivity and specificity of methods, all of which handled the baseline and macromolecules in the GABA spectra differently. Overall, the approaches using

Evidence is accumulating to support the hypothesis that some animals use light-induced radical pairs to detect the direction of the Earth's magnetic field. Cryptochrome proteins seem to be involved in the sensory pathway but it is not yet clear if they are the magnetic sensors: they could, instead, …