Assessing high‐intensity focused ultrasound treatment of prostate cancer with hyperpolarized 13C dual‐agent imaging of metabolism and perfusion. (18th July 2018)

• Record Type: Journal Article
• Authors: Lee, Jessie E.; Diederich, Chris J.; Bok, Robert; Sriram, Renuka; Santos, Romelyn Delos; Noworolski, Susan M.; Salgaonkar, Vasant A.; Adams, Matthew S.; Vigneron, Daniel B.; Kurhanewicz, John
• Other Names: Jagannathan Naranamangalam R. guestEditor.
• Is Part Of: NMR in biomedicine. Volume 32:Number 10(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-07-18
• Subjects: HIFU -- hyperpolarized 13C MRI -- prostate cancer -- pyruvate metabolism -- urea perfusion; Nuclear magnetic resonance -- Periodicals; Magnetic Resonance Spectroscopy -- Periodicals; 574
• DOI: 10.1002/nbm.3962
• Languages: English
• ISSNs: 0952-3480

Abstract

Abstract : The goal of the study was to establish early hyperpolarized (HP) 13 C 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 ( 13 C pyruvate and 13 C urea) 13 C MRI/multiparametric 1 H 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 13 C lactate or HP 13 C 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 13 C 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 K trans showed a similar trend to HP 13 C 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 13 C MR measures of perfusion and metabolism in optimizing focal HIFU, either alone or in combination with adjuvant therapy, deserves further testing in future studies. Abstract : Mice with prostate tumors were treated with HIFU, resulting in partial ablations within the tumors. In a single MRI acquisition after the injection of co‐polarized [1‐13C] pyruvate and 13C urea, the region of HIFU‐induced coagulative ablation can be identified by a complete loss of perfusion and metabolism. The recovery of perfusion and metabolism over time in surrounding tissues that received non‐lethal hyperthermic heat doses could be used to identify the best time to apply adjuvant chemo‐ and radiation therapy.