4.4 Article

A method to convert MRI images of temperature change into images of absolute temperature in solid tumours

Journal

INTERNATIONAL JOURNAL OF HYPERTHERMIA
Volume 29, Issue 6, Pages 569-581

Publisher

INFORMA HEALTHCARE
DOI: 10.3109/02656736.2013.790091

Keywords

Heat-targeted drug delivery; low-temperature sensitive liposomes; MRI; thermometry

Funding

  1. US NIH/NCI [CA42745-21, -22, -23]

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Purpose: During hyperthermia (HT), the therapeutic response of tumours varies substantially within the target temperature range (39-43 degrees C). Current thermometry methods are either invasive or measure only temperature change, which limits the ability to study tissue responses to HT. This study combines manganese-containing low temperature sensitive liposomes (Mn-LTSL) with proton resonance frequency shift (PRFS) thermometry to measure absolute temperature in tumours with high spatial and temporal resolution using MRI. Methods: Liposomes were loaded with 300mM MnSO4. The phase transition temperature (T-m) of Mn-LTSL samples was measured by differential scanning calorimetry (DSC). The release of manganese from Mn-LTSL in saline was characterised with inductively coupled plasma atomic emission spectroscopy. A 2T GE small animal scanner was used to acquire dynamic T-1-weighted images and temperature change images of Mn-LTSL in saline phantoms and fibrosarcoma-bearing Fisher-344 rats receiving hyperthermia after Mn-LTSL injection. Results: The Tm of Mn-LTSL in rat blood was 42.9 +/- 0.2 degrees C (DSC). For Mn-LTSL samples (0.06mM-0.5mM Mn2+ in saline) heated monotonically from 30 degrees C to 50 degrees C, a peak in the rate of MRI signal enhancement occurred at 43.1 degrees +/- 0.3 degrees C. The same peak in signal enhancement rate was observed during heating of fibrosarcoma tumours (N 3) after injection of Mn-LTSL, and the peak was used to convert temperature change images into absolute temperature. Accuracies of calibrated temperature measurements were in the range 0.9-1.8 degrees C. Conclusion: The release of Mn2+ from Mn-LTSL affects the rate of MR signal enhancement which enables conversion of MRI-based temperature change images to absolute temperature.

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