Irreversible change in the T1 temperature dependence with thermal dose using the proton resonance frequency-T1 technique

Abstract

Denaturation of macromolecules within the tissues is believed to be the major factor contributing to the damage of tissues upon hyperthermia. As a result, the value of the spin-lattice relaxation time T1 of the tissue water, which is related to the translational and rotational rates of water, represents an intrinsic probe for investigating structural changes in tissues at high temperature. Therefore, the goal of this work is to investigate whether the simultaneous measurement of temperature and T1 using a hybrid proton resonance frequency (PRF)-T1 measurement technique can be used to detect irreversible changes in T1 that might be indicative of tissue damage. A new hybrid PRF-T1 sequence was implemented based on the variable flip angle driven-equilibrium single-pulse observation (DESPOT)1 method from a standard three dimensional segmented echo-planar imaging sequence by alternating two flip angles from measurement to measurement. The structural changes of the heated tissue volumes were analyzed based on the derived T1 values and the corresponding PRF temperatures. Using the hybrid PRF-T1 technique, we demonstrate that the change of spin lattice relaxation time T1 is reversible with temperature for low thermal dose (thermal dose ≤ 240 cumulative equivalent minutes [CEM] 43°C) and irreversible with temperature after significant accumulation of thermal dose in ex vivo chicken breast tissue. These results suggest that the hybrid PRF-T1 method may be a potentially powerful tool to investigate the extent and mechanism of heat damage of biological tissues.

Figure 1

Experiment setup. The chicken breast, sandwiched between the 4-channel receive coils, was placed within the sample holder container. A chimney filled with degassed water ensured an acoustic beam path to the tissue sample. A fiberoptic temperature probe was positioned near the focus to record temperature changes in real time.

Figure 2

Plot of the normalized signal intensity (SI) of the 3D segmented EPI versus the flip angles. The maximum relaxation time T₁ precision is achieved by choosing the flip angles such that: SI(α₁) = SI(α₂) = 71% of the signal intensity at Ernst angle α_E.

Figure 3

Sonication results of chicken breast for experiment 1 run 1 (22 watts). a: Plot of the average absolute temperature versus time of 4 voxels centered at the focus. b: Plot of the relative change of T₁ versus the absolute temperature of the 4 voxels centered at the focus. The precision of the relative change of T₁ is 0.009. c: Plot of the mean thermal dose versus time of the 4 voxels centered at the focus.

Figure 4

Sonication results of chicken breast for experiment 1 run 2 (32 watts). a: Plot of the absolute temperature versus time of 4 voxels centered at the focus. b: Plot of the relative change of T₁ versus the absolute temperature of the 4 voxels centered at the focus. The precision of the relative change of T₁ is 0.014. c: Plot of the mean thermal dose versus the time of the 4 voxels centered at the focus. The arrows on parts b and c indicate the time at which 240 CEM was reached.

Figure 5

Coronal (a) and sagittal (b) planes through the 3D PRF temperature map around the focal spot at the peak temperature in experiment 1 run 2 (32 watts). (c) Corresponding T₁ map of the focal zone at the peak temperature for experiment 1 run 2 (32 watts). (d) Plot of the dose-interval-averaged change of T_1cor versus the thermal dose. T_1cor values were calculated in the volume defined by the black rectangle in (c) (21×21 voxels) over the 5 central slices. For averaging, the thermal dose was subdivided in ten different ranges of dose: [0 50], [50 100], [100 200], [200 240], [240 500], [500 1000], [1000 2000], [2000, 3000], [3000 5000], and [5000 (higher dose)]. The mean value of T_1cor change for the range of thermal dose 5000 and higher is located at the point 6000 CEM on the dose axis for better visualization of all voxels used. The error bars represent the standard error of the mean value of the T_1cor change values averaged in each dose range.

Figure 6

Plot of absolute T₁ with low accumulated thermal dose. a–b: Temperature and T₁ maps of the focal zone for experiment 2 run 9. The black rectangle represents the ROI used to plot figure c and d. c: Plot of average T₁ versus the average absolute temperature of 4 voxels centered at the focus. A series of ten heating and cooling runs were performed at the acoustic powers: 7 watts, 7 watts, 11 watts, 7 watts, 14 watts, 7 watts, 21 watts, 7 watts, 24 watts, and 7 watts. d: Plot of the corresponding thermal dose versus time averaged over the same 4 voxels centered at the focus.

Figure 7

Plot of absolute T₁ after high thermal dose. a–b: Temperature and T₁ maps of the focal zone for experiment 3 run 1. The black rectangle represents the ROI used to plot figure c and d. The ROI was chosen in region where no voxel were heated to boiling temperature. c: Plot of T₁ versus the absolute temperature of 4 voxels at the focus. A series of five heating and cooling runs were performed at the acoustic powers: 27 watts, 39 watts, 39 watts, 39 watts, 39 watts. d: Plot of the corresponding thermal dose versus time of the 4 voxels centered at the focus.

Figure 8

Distribution of absolute and relative T₁ obtained using Inversion Recovery (IR) and PRF-T₁ in a coronal slice of the chicken breast. a: IR T₁ map before the HIFU heating. b: IR T₁ map of the same coronal slice after the five heating runs in experiment 3 were performed. c: Absolute temperature map of the slice at peak temperature during heating in experiment 3, run 5. d: Cross-section taken centrally through IR T₁ maps before (blue line) and after heating (red dashed line) in experiment 3. The local drop in T₁ corresponds to the region of heating. e: T₁ change map derived from the PRF-T₁ method after the five heating runs in experiment 3. The T₁ changes map was obtained by subtracting the first time frame of run 1 from the last time frame of run 5. f: Corresponding thermal dose map of the same coronal slice. The local drop in T₁ corresponds to the region of heating as shown by the thermal dose map. Sagittal (g–h) through the 3D relative T₁ and thermal dose maps derived from the PRF-T₁ method. i: Picture of the chicken breast after the 5 runs of experiment 3. The color of the chicken breast tissue changed from light pink to white. The color change was the visual indicator that tissue damage has occurred.