Correlation of BOLD MRI with measures of tumor hypoxia in prostate cancer
Bibliographic record
Abstract
Introduction: Tumor oxygen concentrations have prognostic and therapeutic implications in men with prostate cancer. A priori information on tumor oxygenation can be derived by using either Eppendorf measurements or taking additional biopsies after 2-nitroimidazole administration. However, widespread application of these techniques is limited as they are invasive and fail to provide spatial/volumetric information. Blood Oxygen Level Dependent (BOLD) MRI has been proposed for noninvasive three-dimensional characterization of oxygenation. This promising technique requires development and validation against gold-standard measures of tissue hypoxia. This preliminary study was conducted to explore the potential relationship between BOLD MRI, polarographic oxygen electrode measurements, and immunohistochemical evaluation of biopsy specimens. Material and Methods: 15 men with organ confined prostate cancer were enrolled in a prospective clinical trial of BOLD MRI acquisition. Nine men who received both BOLD MRI and Eppendorf measurements were evaluated, including 5 patients who also consented to additional needle-core biopsy immediately after the Eppendorf procedure. 2D gradient echo BOLD images were obtained (2DSPGR) using a torso phased array coil on a 1.5T MRI system with the following parameters: field of view 24cm, matrix 256×192, slice thickness/gap 8/2mm, TR/TE 100/5, 15, 25, 35 and 75ms, bandwidth 31.25kHz, flip angle 40°. From these an R2* map was generated. Using T2 weighted images an expert GU radiologist delineated regions of interest (ROI) suspicious for tumor. and the median R2* of the ROI was calculated. After MRI, transrectal ultrasound guided Eppendorf oxygen measurements were obtained from 4 different tracks within the tumor. Median pO2 and hypoxic fraction <5mm Hg (HP5) was measured. Spearman rho correlation was determined between median pO2, HP5 and R2*. Frozen biopsy tissue was immunostained for CA IX, HIF 1 alpha and GLUT 1 protein expression using antibody concentration of 1:100,1:100 and 1:1000 respectively. Protein expression was evaluated as a function of median pO2, HP5, and median R2*. Results: 8 out of 9 men had low-intermediate risk prostate cancer with median prostate volume of 44 cc (26–60 cc) and median PSA of 7ng/ml (5.5–16). A total of 756 pO2 measurements were obtained with a median pO2 of 8.3mm Hg (0–47.8mm Hg) and median HP5 of 21.4% (0–83.3%). The median R2* was 1712 (842–2307). Correlation was observed between HP5 and R2* (R2=0.80, p=0.01), and between pO2 and R2* (R2=–0.68, p=0.04). While GLUT 1 and HIF 1 expression was observed in all patients, CA IX was expressed only in one patient with the highest HP5 (77%), pO2 (1.40mm Hg), and second highest median R2* (1712). Discussion: In a preliminary evaluation, correlation between R2* and measures of tumor hypoxia (HP5, median pO2, and CAIX expression) is observed. These findings suggest that BOLD MRI may be a biomarker of hypoxia in prostate cancer, warranting further investigation. Future work will develop more robust and quantitative MRI methodologies, and validate such metrics with improved spatial-temporal registration of gold-standard measures of tissue hypoxia.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".