Search Results (5)

Atlantic White Cedar (Chamaecyparis thyoides) (AWC) anchors a globally threatened ecosystem that is being impacted by climate change, as these trees are vulnerable to hurricane events, sea-level rises, and increasing salinity at the forest–marsh ecotone. In this study, we determined the current amount and distribution of AWC in an area that is experiencing sea-level rises that are higher than the global average rate. We used a combination of a field investigation and aerial photo interpretation to identify known locations of AWC, then integrated Sentinel-1 and 2A satellite data with abiotic variables into a species distribution model. We developed a spectral signature of AWC to aid in our understanding of phenology differences from nearby species groups. The selected model had an out-of-bag error of 7.2%, and 8 of the 11 variables retained in the final model were derived from remotely sensed data, highlighting the importance of including temporal data to exploit divergent phenology. Model predictions were strong in live AWC stands and, accurately, did not predict live AWC in stands that experienced high levels of mortality after Hurricane Sandy. The model presented in this study provides high utility for AWC management and tracking mortality dynamics within stands after disturbances such as hurricanes. Full article

Acidification of cancerous tissue induced pharmacologically may slow tumor growth and can be detected using magnetic resonance imaging. Numerous studies have shown that pharmacologically inhibiting specific transporters, such as the Na⁺/H⁺ exchanger 1 (NHE1), can alter glycolitic metabolism and affect tumor acidosis. The sodium proton exchanger inhibitor Cariporide can acidify U87MG gliomas in mice. This study aimed to determine whether Cariporide could acidify C6 glioma tumors in rats with an intact immune system. C6 glioma cells were implanted in the right brain hemisphere of ten rats. Chemical exchange saturation transfer (CEST) MRI (9.4T) was acquired on days 7–8 and 14–15 after implantation to measure in vivo tissue intracellular pH (pH_i) within the tumors and on the contralateral side. pH_i was basic relative to contralateral tissue at both time points assessed using the amine and amide concentration-independent detection (AACID) value. On day 14–15, measurements were made before and up to 160 min after Cariporide injection (N = 6). Twenty minutes after drug injection, the average AACID value in the tumor significantly increased by ∼6.4% compared to pre-injection, corresponding to 0.31 ± 0.20 lower pH_i, while in contralateral tissue, AACID value increased significantly by ∼4.3% compared to pre-injection, corresponding to 0.22 ± 0.19 lower pH_i. Control rats without tumors showed no changes following injection of Cariporide dissolved in 10% or 1% DMSO and diluted in PBS. This study demonstrates the sensitivity of CEST-based pH-weighted imaging for monitoring the response of tumors to pharmacologically induced acidification. Full article

This study shows the use of hyperpolarized ¹³C magnetic resonance spectroscopic imaging (MRSI) to assess therapeutic efficacy in a preclinical tumor model. ¹³C-labeled pyruvate was used to monitor early changes in tumor metabolism based on the Warburg effect. High-grade malignant tumors exhibit increased glycolytic activity and lactate production to promote proliferation. A rodent glioma model was used to explore altered lactate production after therapy as an early imaging biomarker for therapeutic response. Rodents were surgically implanted with C6 glioma cells and separated into 4 groups, namely, no therapy, radiotherapy, chemotherapy and combined therapy. Animals were imaged serially at 6 different time points with magnetic resonance imaging at 3 T using hyperpolarized [1-¹³C]pyruvate MRSI and conventional ¹H imaging. Using hyperpolarized [1-¹³C]pyruvate MRSI, alterations in tumor metabolism were detected as changes in the conversion of lactate to pyruvate (measured as Lac/Pyr ratio) and compared with the conventional method of detecting therapeutic response using the Response Evaluation Criteria in Solid Tumors. Moreover, each therapy group expressed different characteristic changes in tumor metabolism. The group that received no therapy showed a gradual increase of Lac/Pyr ratio within the tumor. The radiotherapy group showed large variations in tumor Lac/Pyr ratio. The chemo- and combined-therapy groups showed a statistically significant reduction in tumor Lac/Pyr ratio; however, only combined therapy was capable of suppressing tumor growth, which resulted in low endpoint mortality rate. Hyperpolarized ¹³C MRSI detected a prompt reduction in Lac/Pyr ratio as early as 2 days post combined chemo- and radiotherapies. Full article

Glioblastoma multiforme (GBM) is the most common primary brain tumor, with most patients dying within 15–18 months of diagnosis despite aggressive therapy. Preclinical GBM models are valuable for exploring GBM progression and for evaluating new therapeutics or imaging approaches. The rat C6 glioma model shares similarities with human GBM, and application of noninvasive imaging enables better study of disease progression. Here, multiparametric magnetic resonance imaging (mpMRI) and bioluminescence imaging (BLI) were applied to characterize longitudinal development of orthotopic luciferase-expressing C6 tumors. Across all rats (n = 11), a large variability was seen for BLI signal, a relative measure of C6 cell viability, but in most individuals, BLI signal peaked at day 11 and decreased thereafter. T2 and contrast-enhanced T1 tumor volumes significantly increased over time (P < .05), and volume measures did not correlate with BLI signal. After day 11, tumor regions of noncontrast enhancement appeared in postcontrast T1-weighted magnetic resonance imaging, and had significantly higher apparent diffusion coefficient values compared with contrast-enhanced regions (P < .05). This suggests formation of ill-perfused, necrotic regions beyond day 11, which were apparent at end-point–matched tissue sections. Our study represents the first combined use of BLI and mpMRI to characterize the progression of disease in the orthotopic C6 rat model, and it highlights the variability in tumor growth, the complementary information from BLI and mpMRI, and the value of multimodality imaging to better characterize tumor development. Future application of these imaging tools will be useful for evaluation of treatment response, and should be pertinent for other preclinical models. Full article

This study presents the first longitudinal measurement of the intracellular/extracellular pH gradient in a rat glioma model using noninvasive magnetic resonance imaging. The acid–base balance in the brain is tightly controlled by endogenous buffers. Tumors often express a positive pH gradient (pH_i – pH_e) compared with normal tissue that expresses a negative gradient. Alkaline pH_i in tumor cells increases activity of several enzymes that drive cellular proliferation. In contrast, acidic pH_e is established because of increased lactic acid production and subsequent active transport of protons out of the cell. pH_i was mapped using chemical exchange saturation transfer, whereas regional pH_e was determined using hyperpolarized ¹³C bicarbonate magnetic resonance spectroscopic imaging. pH_i and pH_e were measured at days 8, 12, and 15 postimplantation of C6 glioma cells into rat brains. Measurements were made in tumors and compared to brain tissue without tumor. Overall, average pH gradient in the tumor changed from −0.02 ± 0.12 to 0.10 ± 0.21 and then 0.19 ± 0.16. Conversely, the pH gradient of contralateral brain tissue changed from −0.45 ± 0.16 to −0.25 ± 0.21 and then −0.34 ± 0.25 (average pH ± 1 SD) Spatial heterogeneity of tumor pH gradient was apparent at later time points and may be useful to predict local areas of treatment resistance. Overall, the intracellular/extracellular pH gradients in this rat glioma model were noninvasively measured to a precision of ∼0.1 pH units at 3 time points. Because most therapeutic agents are weak acids or bases, a priori knowledge of the pH gradient may help guide choice of therapeutic agent for precision medicine. Full article