Detection of Inflammatory Arthritis by Using Hyperpolarized¹³C-Pyruvate with MR Imaging and Spectroscopy

Abstract

Purpose:To examine the feasibility of using magnetic resonance (MR) spectroscopy with hyperpolarized carbon 13 ( 13 C)-labeled pyruvate to detect infl ammation. Materials and Methods:The animal care and use committee approved all work with animals. Arthritis was induced in the right hind paw of six rats; the left hind paw served as an internal control. The lactate dehydrogenase-catalyzed conversion of pyruvate to lactate was measured in infl amed and control paws by using 13 C MR spectroscopy. Clinical and histologic data were obtained to confi rm the presence and severity of arthritis. Hyperpolarized 13 C-pyruvate was intravenously injected into the rats before simultaneous imaging of both paws with 13 C MR spectroscopy. The Wilcoxon signed rank test was used to test for differences in metabolites between the control and arthritic paws.

Increased hyperpolarized [1‐13C] lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized 13C‐labelled bicarbonate

“…Measurements of lactate labelling in animals injected with hyperpolarized [1‐ 13 C]pyruvate have been used previously to assess glycolytic activity in inflamed joints 39. MacKenzie et al39 measured a [1‐ 13 C]lactate/[1‐ 13 C]pyruvate ratio of 0.52 ± 0.16 in CFA‐inflamed rat paws at 20 s after injection of hyperpolarized [1‐ 13 C]pyruvate as compared with a value of 0.74 ± 0.32 (mean ± standard deviation from all image voxels of two inflamed feet, one each from two mice) measured here in CFA‐inflamed mouse paws, also at 20 s after injection.…”

“…MacKenzie et al39 measured a [1‐ 13 C]lactate/[1‐ 13 C]pyruvate ratio of 0.52 ± 0.16 in CFA‐inflamed rat paws at 20 s after injection of hyperpolarized [1‐ 13 C]pyruvate as compared with a value of 0.74 ± 0.32 (mean ± standard deviation from all image voxels of two inflamed feet, one each from two mice) measured here in CFA‐inflamed mouse paws, also at 20 s after injection. The considerable variation in the [1‐ 13 C]lactate/[1‐ 13 C]pyruvate ratio observed here (Figure 2), when compared with the rat model, reflects the small size of the mouse paw, particularly the non‐inflamed paw, which led to relatively low signal‐to‐noise ratios in the 13 C spectra.…”

“…The exchange rate is, in part, dependent on the size of the regional lactate pool47, 48 and therefore is indicative of increased glycolytic activity in inflamed tissue. MacKenzie et al39 showed marked infiltration of leukocytes in the majority of rats with CFA‐induced hind paw inflammation, with accumulation of inflammatory cells at sites of injection. Leukocytes become increasingly glycolytic on activation as do stromal cells, such as fibroblast‐like synoviocytes in RA 49.…”

Hyperpolarized 13 C MR metabolic imaging can detect neuroinflammation in vivo in a multiple sclerosis murine model

“…To date, 13 C MRSI of HP [1-13 C]pyruvate has only been applied to investigate inflammation in three studies: a rat model of radiationinduced lung injury (34), a mouse model of inflammatory arthritis (35), and a mouse model of acute liver injury (36). In all three cases, 13 C MRSI of HP [1-13 C]pyruvate was capable of detecting an increase in the HP [1-13 C]lactate-to-pyruvate ratio in the inflammatory region, which was associated with an increased number of macrophages as detected by H&E staining.…”

Magnetic resonance imaging with hyperpolarized [1,4- 13 C 2 ]fumarate allows detection of early renal acute tubular necrosis

“…Of note, LDH lost from tubular cells is detectable in the urine in patients with ATN (24,25). In contrast, in a rodent arthritis model, there was an increase in [1-13 C]lactate signal in inflamed tissues (26). Given the potential of both hyperpolarized [1,[4][5][6][7][8][9][10][11][12][13] (28)].…”