Concurrent functional and metabolic assessment of brain tumors using hybrid PET/MR imaging.

To evaluate diagnostic accuracy of perfusion weighted imaging (PWI) and positron emission tomography (PET) using an integrated PET/MR system in tumor grading as well as in differentiating recurrent tumor from treatment-induced effects (TIE) in brain tumor patients. Twenty patients (Group A: treatment naïve, 9 patients with 16 lesions; Group B: post-therapy, 11 patients with 18 lesions) underwent fluorine 18 ((18)F) fluorodeoxyglucose (FDG) brain PET/MR with PWI. Two blinded readers predicted low versus high-grade tumor (for Group A) and tumor recurrence versus TIE (for Group B) based solely on tumor rCBV (regional cerebral blood volume) and SUV (standardized uptake values). Tumor histopathology at resection was the reference standard. Using rCBV(mean) ≤ 1.74 as a cut-off, 100% sensitivity and 74% specificity were observed, whereas 75% sensitivity and 89.7% specificity were observed with SUV(mean) ≤ 4.0 as a cut-off to classify patients as test positive for low-grade tumors (Group A) and TIE (Group B). Diagnostic accuracy for detection of low-grade tumors was 90% using PWI and 40% using PET in Group A (p = 0.056); for detection of TIE in Group B, diagnostic accuracy was 94.1% using PWI and 55.6% using PET (p = 0.033). No significant correlation was demonstrated between rCBV parameters and SUV in Group A (mean values: p > 0.403), Group B (p > 0.06) and in the entire population (p > 0.07). Best overall sensitivity and specificity were obtained using rCBV(mean) ≤ 1.74 and SUV(mean) ≤ 4.0 cut-off values. PWI demonstrated better diagnostic accuracy in both groups. Poor correlation was observed between FDG and rCBV parameters.

Does normalisation improve the diagnostic performance of apparent diffusion coefficient values for prostate cancer assessment? A blinded independent-observer evaluation.

AIM: To evaluate the performance of normalised apparent diffusion coefficient (ADC) values for prostate cancer assessment when performed by independent observers blinded to histopathology findings. MATERIALS AND METHODS: Fifty-eight patients undergoing 3 T phased-array coil magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI; maximal b-value 1000 s/mm(2)) before prostatectomy were included. Two radiologists independently evaluated the images, unaware of the histopathology findings. Regions of interest (ROIs) were drawn within areas showing visually low ADC within the peripheral zone (PZ) and transition zone (TZ) bilaterally. ROIs were also placed within regions in both lobes not suspicious for tumour, allowing computation of normalised ADC (nADC) ratios between suspicious and non-suspicious regions. The diagnostic performance of ADC and nADC were compared. RESULTS: For PZ tumour detection, ADC achieved significantly higher area under the receiver operating characteristic curve (AUC; p=0.026) and specificity (p=0.021) than nADC for reader 1, and significantly higher AUC (p=0.025) than nADC for reader 2. For TZ tumour detection, nADC achieved significantly higher specificity (p=0.003) and accuracy (p=0.004) than ADC for reader 2. For PZ Gleason score >3+3 tumour detection, ADC achieved significantly higher AUC (p=0.003) and specificity (p=0.005) than nADC for reader 1, and significantly higher AUC (p=0.023) than nADC for reader 2. For TZ Gleason score >3+3 tumour detection, ADC achieved significantly higher specificity (p=0.019) than nADC for reader 1. CONCLUSION: In contrast to prior studies performing unblinded evaluations, ADC was observed to outperform nADC overall for two independent observers blinded to the histopathology findings. Therefore, although strategies to improve the utility of ADC measurements in prostate cancer assessment merit continued investigation, caution is warranted when applying normalisation to improve diagnostic performance in clinical practice.

Performance of multidetector CT in the evaluation of the endometrium: Measurement of endometrial thickness and detection of disease.

AIM: To evaluate the performance of multidetector computed tomography (MDCT) in the measurement of endometrial thickness and assessment for endometrial disease. MATERIALS AND METHODS: Seventy-nine MDCT examinations, including sagittal reformats from isotropic data, were retrospectively evaluated for the presence of endometrial abnormality, endometrial thickness, and recommendation for transvaginal ultrasound (TVUS) after CT. The endometrial thickness was measured on sagittal images using two different methods, between the inner-to-inner hypoattenuating stripe, and when visible, between the outer-to-outer hyperattenuating stripe. TVUS performed within 48 h of CT in premenopausal and 1 month in postmenopausal patients served as reference standard. Interobserver agreement for endometrial thickness and abnormalities was assessed using concordance correlation (CC) and kappa statistics. RESULTS: Interobserver agreement for endometrial thickness on sagittal CT images was excellent (CC 0.98), and highly accurate using the inner-to-inner measurement. For determination of abnormal thickening, the positive predictive value and negative predictive value were 67-100% and 99.5-100%. For detection of any endometrial abnormality, the positive predictive value and negative predictive value were 79-90% and 84-95%, respectively. False-negative missed abnormalities included small volume hydrometra, a polyp, and endometrial distortion by a fibroid. CONCLUSION: At MDCT, sagittal reformatted images provide reliable endometrial measurement using the inner-to-inner hypoattenuating stripe and are accurately categorized as normal or abnormal thickness using the same numerical criteria as at sonography.

Impact of delay after biopsy and post-biopsy haemorrhage on prostate cancer tumour detection using multi-parametric MRI: a multi-reader study.

AIM: To assess impact of haemorrhage and delay after biopsy on prostate tumour detection using multi-parametric (MP) magnetic resonance imaging (MRI) assessment. MATERIALS AND METHODS: Forty-four patients underwent prostate MRI at 1.5 T using a pelvic phased-array coil, including T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and dynamic contrast-enhanced (DCE) imaging, before prostatectomy. Three radiologists independently reviewed images during four sessions [T2WI, DWI, DCE, and all parameters combined (MP-MRI)] to assess for tumour in each sextant. In a separate session, readers reviewed T1WI to score the extent of haemorrhage per sextant. Accuracy was assessed using logistic regression for correlated data. RESULTS: There was no significant difference in accuracy between readers for any session (p ≥ 0.166), and results were averaged across the three readers for remaining comparisons. Accuracy was significantly greater for MP-MRI than for any parameter alone (p ≤ 0.020). For T2WI alone, there was a trend toward decreased sensitivity in sextants with extensive haemorrhage (p = 0.072). However, accuracy, sensitivity, and specificity were otherwise similar for sextants with and without extensive haemorrhage for all sessions (p = 0.192-0.934). No session showed a significant improvement in accuracy, sensitivity, or specificity in cases with delay after biopsy of over 4 weeks compared with shorter delay. CONCLUSION: Extensive haemorrhage and short delay after biopsy did not negatively impact accuracy for tumour detection using MP-MRI. Further studies using MP-MRI protocols and interpretation schemes from other institutions are required to confirm these observations.

Brain iron quantification in mild traumatic brain injury: a magnetic field correlation study.

BACKGROUND AND PURPOSE: Experimental studies have suggested a role for iron accumulation in the pathology of TBI. Magnetic field correlation MR imaging is sensitive to the presence of non-heme iron. The aims of this study are to 1) assess the presence, if any, and the extent of iron deposition in the deep gray matter and regional white matter of patients with mTBI by using MFC MR imaging; and 2) investigate the association of regional brain iron deposition with cognitive and behavioral performance of patients with mTBI. MATERIALS AND METHODS: We prospectively enrolled 28 patients with mTBI. Eighteen healthy subjects served as controls. The subjects were administered the Stroop color word test, the Verbal Fluency Task, and the Post-Concussion Symptoms Scale. The MR imaging protocol (on a 3T imager) consisted of conventional brain imaging and MFC sequences. After the calculation of parametric maps, MFC was measured by using a region of interest approach. MFC values across groups were compared by using analysis of covariance, and the relationship of MFC values and neuropsychological tests were evaluated by using Spearman correlations. RESULTS: Compared with controls, patients with mTBI demonstrated significant higher MFC values in the globus pallidus (P = .002) and in the thalamus (P = .036). In patients with mTBI, Stroop test scores were associated with the MFC value in frontal white matter (r = -0.38, P = .043). CONCLUSIONS: MFC values were significantly elevated in the thalamus and globus pallidus of patients with mTBI, suggesting increased accumulation of iron. This supports the hypothesis that deep gray matter is a site of injury in mTBI and suggests a possible role for iron accumulation in the pathophysiological events after mTBI.

Breath-hold T2-weighted MRI of the liver at 3T using the BLADE technique: impact upon image quality and lesion detection.

AIM: To compare image quality and lesion detection in the liver using magnetic resonance imaging (MRI) at 3T between T2-weighted imaging using a standard rectilinear k-space trajectory (standard T2WI) and using the BLADE technique (BLADE-T2WI), a technique that employs periodically rotated overlapping parallel lines with enhanced reconstruction for motion correction. MATERIALS AND METHODS: Twenty-eight consecutive patients who underwent MRI examination of the liver at 3T including standard T2WI and BLADE-T2WI, both performed using multiple breath-holds, comprised the study cohort. Images were reviewed in consensus by two radiologists during separate sessions for a number of measures regarding artefacts and image quality. These two readers also assessed the two image sets for the presence of liver lesions and measured liver-to-lesion contrast. Binary logistic regression for correlated data was used to compare the sequences in terms of sensitivity and positive predictive value (PPV) for lesion detection. RESULTS: BLADE-T2WI received significantly higher scores than did standard T2WI for in-plane respiratory motion (p=0.0195), other ghosting artefacts (p<0.0001), sharpness of the liver edge (p=0.0004), sharpness of intra-hepatic vessels (p<0.0001), flow signal suppression (p<0.0001), and overall image quality (p<0.0001). There was a non-significant trend toward improved B(1)-inhomogeneity artefact with BLADE-T2WI (p=0.0571). There was no difference in through-plane respiratory motion (p=0.6836). BLADE-T2WI demonstrated a significant improvement in PPV for lesion detection (p=0.0129) as well as in liver-to-lesion contrast (p=0.0054). There was no difference regarding lesion sensitivity (p=1.0). CONCLUSIONS: Use of the BLADE technique for T2-weighted MRI of the liver at 3T may lead to a significant improvement in image artefacts and improved PPV for lesion detection.

Predicting grade of cerebral glioma using vascular-space occupancy MR imaging.

BACKGROUND AND PURPOSE: MR imaging can measure tissue perfusion and the integrity of the blood-brain barrier. We hypothesize that a combined measure of cerebral blood volume and vascular permeability using vascular-space occupancy (VASO) MR imaging, a recently developed imaging technique, is of diagnostic value for predicting tumor grade. MATERIALS AND METHODS: Thirty-nine patients (9 World Health Organization [WHO] grade II, 20 grade III, and 10 grade IV as determined by histopathologic assessment) were examined using VASO MR imaging, and regions-of-interest analysis was performed in tumoral regions, as well as in regions contralateral to the tumor. A Mann-Whitney test was conducted on the resulting VASO indices for a pairwise comparison across tumor grades. Nominal logistic regression was used to evaluate the use of VASO parameters for predicting group membership (by the percentage of correct classifications). RESULTS: The ratio between tumor side and contralateral side, VASO(Ratio), showed significant differences in all 3 of the pairwise comparisons (P < .01). VASO values in the tumoral regions, VASO(Tumor), showed significant difference between grade II and III and between II and IV but not between III and IV. Both VASO(Tumor) and VASO(Ratio) were found to be significant predictors of tumor grade, giving diagnostic accuracies of 66.7% and 71.8%, respectively. When testing to discriminate grade II tumors from higher grade tumors, the areas under the receiver operating characteristic curve were found to be 0.974 and 0.985 for VASO(Tumor) and VASO(Ratio), respectively. CONCLUSION: VASO MR imaging can be used for noninvasive tumor grade prediction based on cerebral blood volume and vascular permeability. VASO is more effective in separating WHO grade II from higher grades than in separating grade III from grade IV.

Quantitative assessment of iron accumulation in the deep gray matter of multiple sclerosis by magnetic field correlation imaging.

BACKGROUND AND PURPOSE: Deposition of iron has been recognized recently as an important factor of pathophysiologic change including neurodegenerative processes in multiple sclerosis (MS). We propose that there is an excess accumulation of iron in the deep gray matter in patients with MS that can be measured with a newly developed quantitative MR technique--magnetic field correlation (MFC) imaging. MATERIALS AND METHODS: With a 3T MR system, we studied 17 patients with relapsing-remitting MS and 14 age-matched healthy control subjects. We acquired MFC imaging using an asymmetric single-shot echo-planar imaging sequence. Regions of interest were selected in both deep gray matter and white matter regions, and the mean MFC values were compared between patients and controls. We also correlated the MFC data with lesion load and neuropsychologic tests in the patients. RESULTS: MFC measured in the deep gray matter in patients with MS was significantly higher than that in the healthy controls (P < or = .03), with an average increase of 24% in the globus pallidus, 39.5% in the putamen, and 30.6% in the thalamus. The increased iron deposition measured with MFC in the deep gray matter in the patients correlated positively with the total number of MS lesions (thalamus: r = 0.61, P = .01; globus pallidus: r = 0.52, P = .02). A moderate but significant correlation between the MFC value in the deep gray matter and the neuropsychologic tests was also found. CONCLUSION: Quantitative measurements of iron content with MFC demonstrate increased accumulation of iron in the deep gray matter in patients with MS, which may be associated with the disrupted iron outflow pathway by lesions. Such abnormal accumulation of iron may contribute to neuropsychologic impairment and have implications for neurodegenerative processes in MS.

The cochlear-carotid interval: anatomic variation and potential clinical implications.

BACKGROUND AND PURPOSE: A temporal bone CT study in a patient with episodic mid-tone sensorineural hearing loss and tinnitus demonstrated absence of bone between the petrous internal carotid artery and the basal turn of the cochlea. The potential implications with respect to increasingly popular cochlear implant surgery compelled us to retrospectively analyze a series of temporal bone CT scans to establish typical measurements for this region, which we termed the "cochlear-carotid interval" (CCI). METHODS: After IRB exemption, 2 observers independently measured the bony interval between the cochlea and the petrous internal carotid artery canal on coronal images from 30 consecutive temporal bone CT studies. The 1-mm thick coronal images were either acquired directly or were reconstructed from an axial dataset acquired at 0.75 or 0.6 mm section thickness. All measurements were performed by using electronic calipers on a Sienet MagicView VE 42 Siemens PACS station. Mixed model analysis of variance was used to evaluate differences between readers and sides with respect to the mean CCI but adjusted for age and accommodating the correlation among observations generated for the same subject. RESULTS: The patient in our case report had a right CCI of 0.2 mm and left CCI of 0.0 mm. In the other 30 patients, the right CCI ranged from 0.2 to 3.8 mm (mean, 1.2 +/- 0.8 mm; median, 0.9) and the left CCI from 0.2 to 5.0 mm (mean, 1.1 +/- 0.9 mm; median, 0.8). The CCI did not exhibit a significant association with subject age (P = .1336), and there were no significant differences between readers (P = .824) or sides (P = .350) in terms of mean CCI. CONCLUSION: The CCI varies widely between patients and may be as small as zero. Analysis of anatomic relationships suggests a potential relationship between small CCI and mid-tone sensorineural hearing loss, as in our reported patient. Preoperative knowledge of thin or absent bone between the cochlea and petrous carotid canal may help prevent inadvertent penetration of the carotid canal during cochlear implant surgery.

Differential stromal and epithelial localization of cyclooxygenase-2 (COX-2) during colorectal tumorigenesis.

The purpose of the following study is to describe the localization of COX-2 protein and COX-2 mRNA during human colorectal tumorigenesis and to identify potential cellular targets for COX-2 inhibition in chemopreventive strategies. Immunohistochemistry with digital image analysis was used to determine COX-2 protein expression in histologic sections containing synchronous normal colorectal mucosa, adenomas and carcinomas, from 17 previously untreated patients. Epithelial and stromal COX-2 mRNA expression was analyzed by reverse transcription-polymerase chain reaction (RT-PCR), on laser-capture microdissected samples from the same histologies. The stromal compartment in normal colorectal mucosa and adenomas showed higher levels of COX-2 protein expression compared to colorectal carcinomas (p < .0001). Conversely, epithelial COX-2 protein was significantly increased only after development of the invasive phenotype (p < .0001). RT-PCR demonstrated higher stromal COX-2 mRNA expression compared to that within the epithelium for colorectal adenomas and carcinomas. In conclusion, stromal COX-2 may be the target for chemopreventive agents in the early stages of colorectal carcinogenesis.

Quantifying radiation therapy-induced brain injury with whole-brain proton MR spectroscopy: initial observations.

PURPOSE: To quantify the extent of neuronal cell loss imparted to the brain by means of radiation therapy through the decline of the amino acid derivative N-acetylaspartate (NAA) by using proton (hydrogen 1) magnetic resonance (MR) spectroscopy. MATERIALS AND METHODS: Proton MR spectroscopy in a clinical MR imager was used to ascertain the amount of whole-brain NAA before and immediately after whole-brain radiation therapy 3-4 weeks later. Eight patients (four women, four men; median age, 55 years; age range, 39-70 years) were studied. All subjects had lung cancer (non-small cell lung cancer [n = 5], small-cell lung cancer [n = 3]) and received either palliative or prophylactic whole-brain radiation therapy. Six of them also underwent a Mini-Mental Status Examination (MMSE) for correlation with the whole-brain NAA. Two-tailed Student t tests were used to evaluate the data. RESULTS: A significant (P = .042) average decline in whole-brain NAA of -0.91 mmol per person was observed in the cohort. No corresponding changes occurred in MMSE scores. There was no significant difference in whole-brain NAA decline between prophylactic and therapeutic whole-brain radiation therapy. CONCLUSION: Since whole-brain NAA loss was detected even when MMSE scores were unchanged, the former seems to be a more sensitive measure of radiation therapy injury than is the latter.

Patient specific dosing in a cancer phase I clinical trial.

Recent improvements in our understanding of drug metabolism have led to the development of anticancer therapies that accommodate patient differences in drug tolerance. Such methods adjust the dose level according to measurable patient characteristics in order to obtain a target drug exposure. This paper describes the utilization of a patient specific dosing scheme in the statistical design of a phase I clinical trial involving patients with advanced adenocarcinomas of gastrointestinal origin. During the trial, dose levels were adjusted according to each patient's pretreatment concentration of an antibody that was shown in preclinical testing to moderate the effect of the agent under investigation. The design of the trial permitted a continual adjustment of the model used to tailor the dose to each patient's individual needs.

Image cytometry of cyclin D1: a prognostic marker for head and neck squamous cell carcinomas.

CCND1 gene amplification and cyclin D1 protein overexpression are indicators for poor prognosis in invasive head and neck carcinomas. Increased CCND1 gene dosage is a more sensitive prognostic factor than protein overexpression as evaluated by conventional immunohistochemical techniques. Qualitative immunohistochemistry cannot distinguish cyclin D1 overexpression accompanied by amplification of the CCND1 gene from overexpression associated with normal CCND1 gene copy number. To improve the sensitivity of cyclin D1 protein determination, we applied quantitative techniques of image analysis to evaluate cyclin D1 in 54 head and neck carcinomas. There was a significantly higher rate of occurrence of adverse events (P = 0.043) among patients with CCND1 gene amplification than among those without gene amplification. There was a strong association between CCND1 gene amplification (as detected by Southern blot analysis) and the highest nuclear score (by image cytometry of the immunostained tumor sections). The predominance of cells in the lowest nuclear score category was significantly associated with normal copy number (P = 0.005). Conversely, the highest nuclear score was a significant predictor of gene dosage (P = 0.02). Similarly, high nuclear score was a good predictor of death as the final outcome of the disease (P = 0.01). Although somewhat less accurate than Southern blotting, image cytometry of immunohistochemical cyclin D1 stain appears to be a promising tool that could be useful for other tumor marker expression studies.

Glatiramer acetate (Copaxone) treatment in relapsing-remitting MS: quantitative MR assessment.

OBJECTIVE: To evaluate the efficacy of glatiramer acetate (GA, Copaxone; Teva Pharmaceutical Industries, Ltd., Petah Tiqva, Israel) by MRI-based measures in patients with relapsing-remitting (RR) MS. METHODS: Twenty-seven patients with clinically definite RR-MS were treated with either 20 mg of GA by daily subcutaneous self-injection (n = 14) or placebo (n = 13) for approximately 24 months. Axial dual-echo fast-spin-echo T2-weighted images and T1-weighted images before and after gadolinium (Gd) were acquired at 1.5 tesla and transferred into an image processing computer system. The main outcome measures were the number of Gd-enhanced T1 and T2 lesions and their volume as well as brain parenchyma volume. RESULTS: The values of age, disease duration, Expanded Disability Status Scale (EDSS) score, the number of T1- and T2-weighted lesions, and their volume were similar between GA- and placebo-receiving groups at the entry of this study. There was a decrease in the number of T1-enhanced lesions (p = 0.03) and a significant percent annual decrease of their volume in GA recipients compared with those of placebo recipients. There were no significant differences between changes in the two groups in the number of T2 lesions and their volume. The loss of brain tissue was significantly smaller in the GA group compared with that of the placebo group. CONCLUSIONS: These results show that GA treatment may decrease both lesion inflammation and the rate of brain atrophy in RR-MS.

Importance of timing and length of administration of angiogenesis inhibitor TNP-470 in the treatment of K12/TRb colorectal hepatic metastases in BD-IX rats.

BACKGROUND: The timing and length of administration of angiogenesis inhibitor TNP-470 was altered to evaluate the effect on disease progression in a rat model of colorectal hepatic metastases. METHODS: Pair-fed BD-IX rats, injected intrasplenically with rat colon adenocarcinoma K12/TRb cells at day 0, were randomized to receive subcutaneous injections of either placebo or 15 mg/kg TNP-470 on alternate days: for 2 weeks beginning 24 hours after tumor inoculation ("Early"), for 4 weeks beginning 24 hours after tumor inoculation ("Prolonged"), or for 2 weeks beginning at day 15 after macroscopic tumor nodules were confirmed ("Delayed"). Response to treatment was evaluated by counting tumor nodules on the surface of the liver at laparotomy on day 14 and 28 after tumor inoculation. The animals were followed for survival and cause of death. RESULTS: Maximal suppression of hepatic metastases at day 28 required 4-week rather than 2-week TNP-470 administration. Prolonged TNP-470 administration resulted in significantly fewer hepatic metastases at day 28 compared to control (P < .05). Early and prolonged TNP-470 improved survival (Wilcoxon test, P < .05) compared with delayed TNP-470 and placebo. Delayed TNP-470 administration did not increase survival or significantly diminish the number of metastases at day 28 compared with placebo. CONCLUSIONS: These data suggest that prolonged adjuvant antiangiogenic therapy may suppress colorectal hepatic micrometastases.

Paradoxical correlations of cyclin-dependent kinase inhibitors p21waf1/cip1 and p27kip1 in metastatic colorectal carcinoma.

The cyclin-dependent kinase inhibitors (CDIs) p27kip1 and p21waf1/cip1 are key cell cycle-negative regulatory enzymes. The objective of this study was to correlate expression of p27kip1 and p21waf1/cip1 with survival, chemotherapy responsiveness, and expression of the proliferation marker Ki-67 in patients with advanced colorectal cancer. Immunohistochemistry was performed with antibodies to p27kip1, p21waf1/cip1, and Ki-67 on samples from 66 patients with metastatic colorectal carcinoma. Interpretation was performed by visual inspection and automated image analysis. Patients who obtained a response to chemotherapy had greater p21waf1/cip1 tumor staining with a mean of 10.0 positive cells/high-powered field, compared with 4.5 positive cells/high-powered field for nonresponders (P = 0.03). A positive Spearman correlation was seen between Ki-67 and p27kip1 (r = 0.48; P = 0.0001), as well as between Ki-67 and p21waf1/cip1 (r = 0.48; P = 0.0001). A trend toward shorter survival was seen in patients with positive specimens (median survival of 10 months for patients with both p27kip1- and p21waf1/cip1-positive specimens, compared with 22 months for patients with neither p27kip1- nor p21waf1/cip1-positive specimens). In contrast to that previously reported in normal colonic mucosa or early-stage colorectal cancer, we observed positive correlations of Ki-67 with both p27kip1 and p21waf1/cip1, a trend toward greater CDI staining indicating worse prognosis, and greater p21waf1/cip1 staining in tumors that were chemosensitive. These findings suggest that in the metastatic setting, CDIs may show altered function, compared with their role in the normal cell cycle.

Polarographic needle electrode measurements of oxygen in rat prostate carcinomas: accuracy and reproducibility.

PURPOSE: The oxygenation status of tumors may be important for predicting tumor response to therapy. Previous studies with the anaplastic (R3327-AT) and well-differentiated (R3327-H) Dunning rat prostate tumors using indirect assays of tumor oxygenation indicated the relative hypoxic and radioresistant nature of the anaplastic tumor. We now report direct measurements of oxygen in these tumors made with the pO2 histograph to determine: (a) whether a significant difference in oxygenation status could be detected between them: (b) whether sequential measurements on the same tumor gave similar values; and (c) whether tumor oxygenation correlated with tumor volume. METHODS AND MATERIALS: R3327-AT and R3327-H tumors were grown in Fischer X Copenhagen rat to volumes of 1.0-7.0 cm3. Electrode measurements (100-200) were made in tumors in anesthetized animals along two parallel tracks. Repeat measurements were made at 1-5 days along different parallel tracks. Oxygen partial pressures of muscle tissue were measured and served as a normal tissue control. Statistical analyses were applied to determine whether tumor oxygen levels were different between the two tumor histologies, whether sequential measurements in the same tumor were reproducible, and whether tumor oxygenation correlated with tumor volume. RESULTS: The average median pO2 of the well-differentiated (n = 15) and the anaplastic (n = 15) tumors was 6.0 mmHg (SE +/- 1.3) and 2.2 mmHg (SE +/- 0.3), respectively. The average median pO2 of normal rat muscle (n = 15) was 23.6 mmHg (SE +/- 2.0). These values represent highly significant differences in oxygen concentration between the two tumors and rat muscle. The differences in average mean pO2 values were also highly significant. Repeat measurements in the same tumors on different days gave average median values of 4.7 and 2.2 mmHg in the R3327-H (n = 15) and R3327-AT (n = 15) tumors, respectively. For these repeat measurements, median pO2 values decreased in 15 and increased in 15 tumors, and were not significantly different from the first measurements. The average differences observed in median pO2 were 37% (SE +/- 7) and 58% (SE +/- 10) for the R3327-H and R3327-AT tumors, respectively. No significant correlation was observed between pO2 levels and the tumor volumes investigated in this study. CONCLUSIONS: The median pO2 values of the anaplastic Dunning tumors were significantly lower than those of the well-differentiated tumors (p < 0.001). Oxygen levels in both tumors were significantly lower than those measured in normal rat muscle (p < 0.00005). Repeat measurements of median pO2 in the same tumors were not significantly different for either tumor model (p > 0.5). The changes observed in pO2 distributions within individual tumors from day to day may indicate true dynamics of its oxygenation status and/or the limits of electrode measurements, by sampling along only two insertion sites. The electrode measurements of pO2 in these tumor models are reproducible and confirm previously detected oxygenation differences between the anaplastic and well-differentiated tumors.