Intermolecular Multiple Quantum Coherences Enable Accurate Thermal Imaging of Red Bone Marrow During Thermal Therapy of Bone Metastases

Prostate and breast cancers are two of the most common types of cancer in the United States, and those cancers metastasize to bone in more than two thirds of patients. Recent evidence suggests that thermal therapy is effective at treating metastatic bone cancer. For example, thermal therapy enables targeted drug delivery to bone, ablation of cancer cells in bone marrow, and palliation of bone pain. Thermal therapy of bone metastases would be greatly improved if it were possible to image the temperature of the tissue surrounding the disease, which is usually red bone marrow (RBM). Unfortunately, current thermal imaging techniques are inaccurate in RBM.

This dissertation shows that many of the difficulties with thermal imaging of RBM can be overcome using a magnetic resonance phenomenon called an intermolecular multiple quantum coherence (iMQC). Herein, iMQCs are detected with a magnetic resonance imaging (MRI) pulse sequence called multi-spin-echo HOMOGENIZED with off resonance transfer (MSE-HOT). Compared to traditional methods, MSE-HOT provided ten-fold more accurate images of temperature change. Furthermore, MSE-HOT was translated to a human MRI scanner, which enabled imaging of RBM temperature during heating with a clinical focused ultrasound applicator. In summary, this dissertation develops a MRI technique that enables thermal imaging of RBM during thermal therapy of bone metastases.

Multifactorial determinants of the neurocognitive effects of electroconvulsive therapy.

For many patients with neuropsychiatric illnesses, standard psychiatric treatments with mono or combination pharmacotherapy, psychotherapy, and transcranial magnetic stimulation are ineffective. For these patients with treatment-resistant neuropsychiatric illnesses, a main therapeutic option is electroconvulsive therapy (ECT). Decades of research have found ECT to be highly effective; however, it can also result in adverse neurocognitive effects. Specifically, ECT results in disorientation after each session, anterograde amnesia for recently learned information, and retrograde amnesia for previously learned information. Unfortunately, the neurocognitive effects and underlying mechanisms of action of ECT remain poorly understood. The purpose of this paper was to synthesize the multiple moderating and mediating factors that are thought to underlie the neurocognitive effects of ECT into a coherent model. Such factors include demographic and neuropsychological characteristics, neuropsychiatric symptoms, ECT technical parameters, and ECT-associated neurophysiological changes. Future research is warranted to evaluate and test this model, so that these findings may support the development of more refined clinical seizure therapy delivery approaches and efficacious cognitive remediation strategies to improve the use of this important and widely used intervention tool for neuropsychiatric diseases.