Proton Resonance Frequency Chemical Shift Thermometry: Experimental Design and Validation toward High-Resolution Noninvasive Temperature Monitoring and In Vivo Experience in a Nonhuman Primate Model of Acute Ischemic Stroke

Linear regression from the DIFF 1 experiment. The y-axis represents the water-NAA chemical shift difference, plotted against continuous fiber optic measured temperatures from approximately 18 to 45°C. The slope of regression, 0.01 ppm/°C, is in agreement with the expected temperature dependency of the temperature-dependent proton chemical shift.

Linear regression from the DIFF 2 experiment. Similar correlation as noted in DIFF 1. By comparison with DIFF 1, approximately 15%–20% time savings is achieved by eliminating the paired approach used in Fig 2.

DIFF 3 versus temperature change. Excellent correlation is again noted between measured temperatures and the water-NAA chemical shift. Frequency shifts are measured from sequential, non-water-suppressed spectra against an initial NAA reference frequency. Elimination of the repeated metabolite spectra in DIFF 1 and DIFF 2 permits increasing temporal resolution, with collection of 102 data points between approximately 18 and 35°C, compared with <15 measures across a similar experimental session.

Single-voxel MR spectroscopy in a healthy nonhuman primate during physiologic monitoring under general anesthesia, with maintenance of rectal temperatures at approximately 37°C. Six repeated MR spectroscopy scans were acquired from the right operculum by using a standard point-resolved spectroscopy sequence across an approximately 3-hour imaging session. Temperatures were computed from the temperature-dependent water-NAA chemical shift difference (see text), with mean computed temperatures of 36.94 ± 0.22°C. Spectral fitted full width at half maximum varies between 4 and 5 Hz.

Multivoxel MR thermometry in a healthy nonhuman primate during physiologic monitoring under general anesthesia, with maintenance of rectal temperatures at approximately 37°C. Six repeated MR spectroscopy scans were acquired by using 2D chemical shift imaging spectroscopy (see text) across an approximately 3-hour imaging session. Computed temperatures are derived from the water-NAA proton chemical shift and color thermal grid overlaid on the axial T2-weighted reference image for display purposes. A relatively symmetric, zonal distribution of temperatures is noted across repeated studies; a representative peripheral voxel demonstrates the repeatability of in vivo imaging, with mean computed temperatures of 37.6 ± 0.02°C. Spectral-fitted full widths at half maximum vary between 4 and 5 Hz across voxels.

A, Single-voxel MR thermometry in an adult nonhuman primate 6 hours following endovascular MCA occlusion. Axial T2-weighted image (right) with symmetric 1.5-mL voxels placed in the bilateral opercular region. B, Area of infarction in the right hemisphere demonstrated on diffusion-weighted images (yellow arrows). Computed temperatures within the region of infarction are noted approaching 0.5°C less than those in the contralateral hemisphere.