Invited Paper BI+AS+IPF+MN-MoA1
NMR Relaxometry as a Medical Diagnostic

Monday, October 22, 2018, 1:20 pm, Room 101B

This talk will describe the diagnostic capabilities of magnetic resonance imaging (MRI) when brought to the patient bedside. Rather than imaging, NMR can be used for important chemical/physiologic diagnostic endpoints. Two will be discussed here; quantifying fluid overload and measurement of hypoxia within tumors. Assessment of intra- and extra-vascular volume is integral in managing patients with heart, liver, and kidney disease as volume status is closely linked to mortality. Commonly used determinants of volume status, such as physical exam and ultrasonography, lack sensitivity and specificity and require expertise in clinical practice. This talk reports on nuclear magnetic resonance (NMR) methods to a portable and clinically useful device. A clinical study with hemodialysis patients and age-matched healthy controls was performed at MGH. The Τ2 relaxation times of study participants’ legs were quantified at multiple time points with both a 1.5T clinical MRI scanner and a custom 0.27T single-voxel MR sensor. The results showed that first sign of fluid overload is an increase in the relative fraction of extracellular fluid in the muscle. The relaxation time of the extracellular fluid in the muscle eventually increases after more fluid is accumulated. Importantly, these MR findings occur before signs of edema are detectable on physical exam. Solid tumors are often hypoxic and characterized by an extreme lack of oxygen. Tumor hypoxia imparts significant negative outcomes for patients but is highly variable within cancer types and patient populations. Many of these poor clinical outcomes can be tied to hypoxic-induced radiotherapy resistance. Resistance to radiotherapy in hypoxic regions can be overcome by increasing the dose delivered but exposure limitations of healthy tissue and organs must be considered. The lack of a viable quantitative clinical oxygen measurement method prevents safe dose escalation in these patient populations. Here we report on a silicone-based quantitative oxygen sensor. The MRI contrast of this material depends on dissolved oxygen. Thus, the material functions as a first of its kind solid-state contrast agent. The sensor leverages the existing MRI hardware, which is part of the current clinical work flow, to map tumor oxygen content. This information can then be integrated into the dose planning process clinicians currently conduct to selectively and safely boost dose to low oxygen tumor subvolumes. This sensor is approved by the institutional review board at Dana Farber Cancer Center for a clinical trial in patients locally advanced cervical cancer.