MR Thermometry in Cerebrovascular Disease: Physiologic Basis, Hemodynamic Dependence, and a New Frontier in Stroke Imaging

Abstract

The remarkable temperature sensitivity of the brain is widely recognized and has been studied for its role in the potentiation of ischemic and other neurologic injuries. Pyrexia frequently complicates large-vessel acute ischemic stroke and develops commonly in critically ill neurologic patients; the profound sensitivity of the brain even to minor intraischemic temperature changes, together with the discovery of brain-to-systemic as well as intracerebral temperature gradients, has thus compelled the exploration of cerebral thermoregulation and uncovered its immutable dependence on cerebral blood flow. A lack of pragmatic and noninvasive tools for spatially and temporally resolved brain thermometry has historically restricted empiric study of cerebral temperature homeostasis; however, MR thermometry (MRT) leveraging temperature-sensitive nuclear magnetic resonance phenomena is well-suited to bridging this long-standing gap. This review aims to introduce the reader to the following: 1) fundamental aspects of cerebral thermoregulation, 2) the physical basis of noninvasive MRT, and 3) the physiologic interdependence of cerebral temperature, perfusion, metabolism, and viability.

Fig 1.

A, Schematic representation of the temperature-dependency of the water proton resonance frequency chemical shift. A water hydrogen bonding scenario for water molecules in two milieu of differing temperatures is depicted. Increasing temperatures drive the water hydrogen bonding equilibrium towards greater free water proportions through disruption of hydrogen bonds. Electronic currents (“e-”) about the hydrogen proton shield it from the main magnetic flux, but will vary in strength between strongly (left) and weakly (right) bound water pools. The greater shielding of free water hydrogens (right) yields lower precessional frequencies, governed by the gyromagnetic ratio of hydrogen, ∼42MHz/T. B, Within the hydrogen PRF spectrum, higher temperatures translate the water resonance upfield (i.e. towards lower chemical shifts), reducing the chemical shift difference between water and a non-temperature dependent reference such as the methyl resonance of NAA, producing a linear correlation coefficient (C) of ∼−0.01 ppm/C. As shown, the relationship between hydrogen bonding equilibrium, PRF, and temperature remains linear across even supraphysiologic temperature ranges as demonstrated in an aqueous cytosolic phantom during real time fiberoptic temperature monitoring. Adapted from Dehkharghani et al.

Fig 2.

Phantom (A) and human in vivo PRF thermometry in a healthy volunteer (B) using the water-NAA chemical shift, demonstrating the impact of adiabatic (semiLASER) versus conventional volume localization (PRESS) and improvements in the shimming conditions using 3D gradient-echo (greSHIM). Spatially uniform phantom temperatures are noted in A with improvements in SNR, fitted line widths, and test-retest repeatability (not shown) by comparison with conventional point-resolved spectroscopy using sLASER at 3T. Greater test-retest stability obtained 30 minutes apart and the presence of physiologically meaningful temperature gradients are demonstrated to greater advantage in the lower row of B when using sLASER for spatial localization together with greSHIM. Adapted from Dehkharghani et al.,^, with permission from the International Society of Magnetic Resonance in Medicine.

Fig 3.

Dynamic MR thermometry following superselective right MCA endovascular stroke induction in an adult rhesus macaque using a low-profile suture embolus. DWI (A) obtained at approximately 7 hours following complete occlusion and contemporaneous 2D axial sLASER chemical shift thermography (see MR Thermometry in Stroke and Cerebrovascular Disease: Acute Ischemic Stroke) following automated and manual shimming (B) demonstrate extensive right-hemispheric ischemic injury and generalized cerebral hyperthermia, respectively. Through the course of the experiment, temperatures in both hemispheres were noted to rise, importantly with a differing temporal course and, in both cases, outpacing the influences of the steadily increasing systemic pyrexia (C), measured continuously from an indwelling rectal probe and aggregated over all subjects. The correlation between both normalized infarction size (C) and time from infarction relative to cerebral temperatures was similarly observed across all experimental NHP strokes, and aggregated results are depicted. Adapted from Dehkharghani et al.

Fig 4.

Cerebrovascular reserve (CVR) percentage augmentation maps calculated with BOLD and arterial spin-labeling (ASL), as well as a BTR map overlaid on a T1-weighted anatomic image. Images are all from the same subject (a 32-year-old woman with unilateral left MCA stenosis and multiple TIAs). The white grid overlay represents the MR thermometry VOI derived from multivoxel spectroscopy analysis using the water-NAA chemical shift difference. Images are displayed in the radiologic convention. Impaired cerebrovascular reserve in the left hemisphere is present in both BOLD and ASL, with a greater severity of impairment in arterial spin-labeling, likely related to tag decay and residual delay sensitivity despite the use of 10 separate, in-line postlabel delays of varying duration. The BTR map demonstrates an asymmetric thermal response, with less brain cooling following vasodilatory stimulus in the diseased left hemisphere, indicated by reduced (ie, less negative) BTR values and corresponding primarily to the areas of greatest impairment in the anterior and posterior MCA borderzone territories. Maximal (most negative) BTRs are noted in the regions spatially concordant with the greatest hemodynamic augmentation (blue regions) in the right parietal lobe. Adapted from Fleischer et al.

Fig 5.

Real-time temperature mapping using phase-based PRF thermometry during stereotactic laser amygdalohippocampectomy for mesial temporal lobe epilepsy. Multiplanar spoiled gradient T1-weighted images obtained with intravenous gadolinium (A and B) demonstrate a stereotactically introduced, right-posterior-approach ablative probe, terminating within the right hippocampal formation. A parametric thermal map with inset scale and a temperature-time course graph (C and D, respectively) demonstrate that the estimated, relative temperature change from baseline following ablation exceeded 30°C. Contrast-enhanced T2-FLAIR axial image (E) through the treatment bed confirms the final zone of ablative injury.