| Abstract: | The goal of the study was to establish early hyperpolarized (HP) 13C MRI metabolic and perfusion changes that predict effective high‐intensity focused ultrasound (HIFU) ablation and lead to improved adjuvant treatment of partially treated regions. To accomplish this a combined HP dual‐agent (13C pyruvate and 13C urea) 13C MRI/multiparametric 1H MRI approach was used to measure prostate cancer metabolism and perfusion 3–4 h, 1 d, and 5 d after exposure to ablative and sub‐lethal doses of HIFU within adenocarcinoma of mouse prostate tumors using a focused ultrasound applicator designed for murine studies. Pathologic and immunohistochemical analysis of the ablated tumor demonstrated fragmented, non‐viable cells and vasculature consistent with coagulative necrosis, and a mixture of destroyed tissue and highly proliferative, poorly differentiated tumor cells in tumor tissues exposed to sub‐lethal heat doses in the ablative margin. In ablated regions, the intensity of HP 13C lactate or HP 13C urea and dynamic contrast‐enhanced (DCE) MRI area under the curve images were reduced to the level of background noise by 3–4 h after treatment with no recovery by the 5 d time point in either case. In the tissues that received sub‐lethal heat dose, there was a significant 60% ± 12.4% drop in HP 13C lactate production and a significant 30 ± 13.7% drop in urea perfusion 3–4 h after treatment, followed by recovery to baseline by 5 d after treatment. DCE MRI Ktrans showed a similar trend to HP 13C urea, demonstrating a complete loss of perfusion with no recovery in the ablated region, while having a 40%–50% decrease 3–4 h after treatment followed by recovery to baseline values by 5 d in the margin region. The utility of the HP 13C MR measures of perfusion and metabolism in optimizing focal HIFU, either alone or in combination with adjuvant therapy, deserves further testing in future studies. |
