Veronica A. Morgan

Diffusion-weighted magnetic resonance imaging: a potential non-invasive marker of tumour aggressiveness in localized prostate cancer

AIM To evaluate diffusion-weighted magnetic resonance imaging (DW-MRI) as a marker for disease aggressiveness by comparing tumour apparent diffusion coefficients (ADCs) between patients with low- versus higher-risk localized prostate cancer. METHOD Forty-four consecutive patients classified as low- [n = 26, stageT1/T2a, Gleason score < or = 6, prostate-specific antigen (PSA)< 10 (group 1)] or intermediate/high- [n = 18, stage > or = T2b and/or Gleason score > or = 7, and/or PSA > 10 (group 2)] risk, who subsequently were monitored with active surveillance or started neoadjuvant hormone and radiotherapy, respectively, underwent endorectal MRI. T2-weighted (T2W) and DW images (5 b values, 0-800 s/mm(2)) were acquired and isotropic ADC maps generated. Regions of interest (ROIs) on T2W axial images [around whole prostate, central gland (CG), and tumour] were transferred to ADC maps. Tumour, CG, and peripheral zone (PZ = whole prostate minus CG and tumour) ADCs (fast component from b = 0-100 s/mm(2), slow component from b = 100-800 s/mm(2)) were compared. RESULTS T2W-defined tumour volume medians, and quartiles were 1.2 cm(3), 0.7 and 3.3 cm(3) (group 1); and 6 cm(3), 1.3 and 16.5 cm(3) (group 2). There were significant differences in both ADC(fast) (1778 +/- 264 x 10(-6) versus 1583 +/- 283 x 10(-6) mm(2)/s, p = 0.03) and ADC(slow) (1379 +/- 321 x 10(-6) versus 1196 +/- 158 x 10(-6) mm(2)/s, p = 0.001) between groups. Tumour volume (p = 0.002) and ADC(slow) (p = 0.005) were significant differentiators of risk group. CONCLUSION Significant differences in tumour ADCs exist between patients with low-risk, and those with higher-risk localized prostate cancer. DW-MRI merits further study with respect to clinical outcomes.

Combined Use of Diffusion-Weighted MRI and 1H MR Spectroscopy to Increase Accuracy in Prostate Cancer Detection

OBJECTIVE The objective of our study was to establish the sensitivity and specificity for prostate cancer detection using a combined 1H MR spectroscopy and diffusion-weighted MRI approach. SUBJECTS AND METHODS Forty-two men (mean age +/- SD, 69.3 +/- 4.7 years) with prostate cancer were studied using endorectal T2-weighted imaging, 2D chemical shift imaging (CSI), and isotropic apparent diffusion coefficient (ADC) maps. Regions of interest (ROIs) were drawn around the entire gland, central gland, and peripheral zone tumor, diagnostically defined as low signal intensity on T2-weighted images within a sextant that was biopsy-positive for tumor. Lack of susceptibility artifact on a gradient-echo B0 map through the slice selected for CSI and no high signal intensity on external array T1-weighted images confirmed the absence of significant hemorrhage after biopsy. CSI voxels were classified as nonmalignant or as tumor (ROI included > or = 30% or > or = 70% tumor). Choline-citrate (Cho/Cit) ratios and average ADCs were calculated for every voxel. A plot of Cho/Cit ratios versus ADCs yielded a line of best separation of tumor voxels from nonmalignant voxels. Receiver operating characteristic (ROC) curves were plotted for Cho/Cit ratios alone, ADCs alone, and a combination of the two. RESULTS The Cho/Cit ratios were significantly higher (p < 0.001) and the ADCs were significantly lower (p < 0.006) in tumor-containing voxels than in non-tumor-containing voxels. When voxels containing 30% or more tumor were considered positive, the area under the ROC curves using combined MR spectroscopy and ADC (0.81) was similar to that of Cho/Cit alone (0.79) and better than ADC alone (0.66). When voxels containing 70% or more tumor were considered positive and cutoffs to achieve a 90%-or-greater sensitivity chosen, a combination of Cho/Cit and ADC achieved a significant improvement in specificity compared with Cho/Cit alone (p < 0.0001) or ADC alone (p < 0.0001). CONCLUSION When voxels containing > or = 70% tumor are considered positive, the combined use of MR spectroscopy and diffusion-weighted MRI increases the specificity for prostate cancer detection while retaining the sensitivity compared with MR spectroscopy alone or diffusion-weighted MRI alone.

A Study of Diffusion-Weighted Magnetic Resonance Imaging in Men with Untreated Localised Prostate Cancer on Active Surveillance

BACKGROUND Markers that predict the behaviour of localised prostate cancer are needed to identify patients that require treatment. OBJECTIVE We have analysed the apparent diffusion coefficient (ADC) generated from diffusion-weighted magnetic resonance imaging (DW-MRI) with respect to repeat biopsy findings and time to radical treatment in patients in a prospective study of active surveillance. DESIGN, SETTING, AND PARTICIPANTS Some 86 men recruited between 2002 and 2006 were followed for a median of 29 mo. Patients had clinical stage T1/T2a N0/Nx M0/Mx adenocarcinoma of the prostate, prostate-specific antigen (PSA) level<15 ng/ml, Gleason score≤7, primary Gleason grade≤3, and positive biopsy cores (pbc)≤50%. MEASUREMENTS All patients had DW-MRI in addition to standard MRI sequences. Tumour regions of interest (ROIs) were identified using T2-weighted fast-spin echo images as focal areas of restricted diffusion. Univariate analyses including all clinical variables and tumour ADC data were performed with respect to repeat biopsy findings and time to radical treatment. Receiver operating curves (ROC) compared predictive variables. RESULTS AND LIMITATIONS Patients in the study had a median age of 66 yr and a median initial PSA level of 6.7 ng/ml. Some 39 patients (45%) received deferred radical treatment, and 34 patients (40%) had adverse histology on repeat biopsy. According to univariate analysis, tumour ADC was a significant predictor of both adverse repeat biopsy findings (p<0.0001; hazard ratio [HR]: 1.3; 95% confidence interval [CI]: 1.1-1.6), and time to radical treatment (p<0.0001; HR: 1.5; 95% CI: 1.2-1.8). ROC curves for ADC showed an area under the curve (AUC) of 0.7 for prediction of adverse repeat biopsy findings and an AUC of 0.83 for prediction of radical treatment. CONCLUSIONS In patients with low-risk, localised disease, tumour ADC on DW-MRI may be a useful marker of prostate cancer progression and may help to identify patients who stand to benefit from radical treatment. This possibility warrants further study.

Diffusion-weighted Imaging in Cervical Cancer with an Endovaginal Technique: Potential Value for Improving Tumor Detection in Stage Ia and Ib1 Disease

PURPOSE To establish apparent diffusion coefficients (ADCs) of invasive cervical carcinoma compared with nontumor cervical epithelium and determine sensitivity and specificity of diffusion-weighted (DW) magnetic resonance (MR) imaging used in conjunction with T2-weighted MR imaging to help detect invasive cervical carcinoma in patients with stage Ia and Ib1 disease. MATERIALS AND METHODS Local research ethics committee approval was obtained with written consent from each subject. Group 1 comprised patients (mean age, 38.7 years +/- 13.2 [standard deviation]) with histologically confirmed cervical intraepithelial neoplasia (CIN) found on smear (n = 20) or stage Ib1 cervical tumors (n = 18). Patients were imaged with endovaginal T2-weighted fast spin-echo and single-shot DW echo-planar MR imaging of the cervix. ADCs from invasive cervical carcinoma and nontumor regions were compared within (t test) and between (U test) patients. A derived threshold ADC level indicative of invasive cervical carcinoma was used with T2-weighted imaging by two independent observers to identify possible invasive cervical carcinoma in group 2, patients with suspected disease (n = 21; mean age, 42.0 years +/- 16.4). Surgical specimens were the reference standard. Interobserver agreement was assessed. RESULTS In group 1, ADCs from cervical carcinoma (757 x 10(-6) mm(2)/sec +/- 110) and adjacent epithelium (1331 x 10(-6) mm(2)/sec +/- 159) or CIN (1291 x 10(-6) mm(2)/sec +/- 156) were significantly different (P < .0001). In group 2, respective sensitivity and specificity to help detect invasive cervical carcinoma on T2-weighted images were 55.6% and 75% for observer 1 and 66.7% and 41.7% for observer 2, and 88.9% and 66.7% for observer 1 and 77.8% and 58.3% for observer 2 when ADC maps with a threshold level of 1100 x 10(-6) mm(2)/sec were added. Interobserver agreement was fair (kappa = 0.37) for T2-weighted images alone and good (kappa = 0.80) with ADC included. CONCLUSION ADCs from invasive cervical carcinoma are significantly lower than those from nontumor epithelium; good interobserver agreement by using T2-weighted and DW MR imaging makes this technique potentially useful to help detect early-stage disease.

MRI in the Detection of Prostate Cancer: Combined Apparent Diffusion Coefficient, Metabolite Ratio, and Vascular Parameters

OBJECTIVE The purpose of this study was to compare apparent diffusion coefficients, metabolic ratios, and vascularity values within histologically defined prostate tumors with those in nontumor tissue to determine which functional parameter or combination of parameters is best for differentiating tumor from nontumor tissue. SUBJECTS AND METHODS Twenty patients due for prostatectomy underwent endorectal MRI at 1.5 T. Transverse T2-weighted, diffusion-weighted, 2D chemical shift, and dynamic contrast-enhanced images were acquired. After prostatectomy, the gland was sectioned transversely. Fresh slices and stained whole-mount sections with histologically defined tumor outlines were photographed. The tumor outlines were mapped onto images, and the apparent diffusion coefficient (ADC), choline-to-citrate (Cho/cit) ratio, and vascularity of the histologically defined tumor, normal peripheral zone, and central gland were quantitatively measured. Area under the receiver operating characteristics (ROC) curve (A(z)) was used to determine the sensitivity and specificity of parameter combinations in cancer detection. RESULTS In tumor regions larger than 1 cm(2), the Cho/cit ratio was higher in tumor than in nontumor tissue (p < 0.001), in the peripheral zone alone (p = 0.007), and in the central gland alone (p = 0.005). ADC was lower and tumor vascularity greater in tumor than in nontumor tissue (ADC, p = 0.003; initial area under the gadolinium plasma concentration-time curve [initial gadolinium AUC], p = 0.012; forward rate constant [K(trans)], p = 0.011; return rate constant [k(ep)], p = 0.036). No single parameter had a significantly greater A(z) (ADC, 0.71; Cho/cit ratio, 0.79; initial gadolinium AUC, 0.60; K(trans), 0.62; k(ep), 0.65). Pairs of parameters, however, did increase A(z): ADC and initial gadolinium AUC (A(z) = 0.94) versus ADC (p = 0.001) and initial gadolinium AUC (p < 0.001); ADC and Cho/cit ratio (A(z) = 0.94) versus ADC (p = 0.001) and Cho/cit ratio (not significant); and Cho/cit ratio and initial gadolinium AUC (A(z) = 0.88) versus Cho/cit ratio (not significant) and initial gadolinium AUC (p < 0.001). All three functional techniques together had an A(z) of 0.95, showing no further improvement. CONCLUSION The combination of two functional parameters is associated with significant improvement in prostate cancer detection over use of any parameter alone. Use of a third parameter does not increase the rate of detection.

Evaluation of the Potential of Diffusion-Weighted Imaging in Prostate Cancer Detection

Background: Conventional T2-weighted (T2W) imaging alone has a poor sensitivity for prostate cancer detection. Purpose: To evaluate combined T2W and diffusion-weighted magnetic resonance imaging (DW-MRI) versus T2W MRI alone for identifying tumor in patients with prostate cancer. Material and Methods: Fifty-four consecutive patients with prostate cancer (46 stage 1 and 2, 8 stage 3) and sextant biopsies within the previous 3 months were studied. Endorectal MR images were analyzed by two radiologists (1 experienced, 1 trainee) blinded to patient information and histopathology. T2W images were scored first, followed by combined T2W and isotropic apparent diffusion coefficient (ADC) maps calculated from DW-MRI (b = 0, 300, 500, and 800 s/mm2). Gland apex, middle, and base for each side were scored negative, indeterminate, or positive for tumor. Imaging data for each sextant were compared with histology. Sensitivity, specificity, and interobserver agreement were calculated. Results: Sensitivity and specificity for tumor identification significantly improved from 50% and 79.6% (T2W alone, experienced observer) to 73.2% and 80.8% (P<0.001), respectively. For the trainee observer, there was no improvement (44.3% and 72% T2W alone vs. 45.1% and 69.2% T2W plus ADC maps). Interobserver agreement was moderate for T2W imaging alone (kappa 0.51) and fair for T2W plus ADC maps (kappa 0.33). Conclusion: In an experienced observer, DW-MRI together with T2W imaging can significantly improve tumor identification in prostate cancer.

Relationship Between Imaging Biomarkers of Stage I Cervical Cancer and Poor-Prognosis Histologic Features: Quantitative Histogram Analysis of Diffusion-Weighted MR Images

OBJECTIVE The purpose of this study was to determine whether histogram analysis of apparent diffusion coefficient (ADC) values from diffusion-weighted MRI can be used to differentiate cervical tumors according to their histologic characteristics. SUBJECTS AND METHODS Sixty patients with International Federation of Gynecology stage I cervical cancer underwent MRI at 1.5 T with a 37-mm-diameter endovaginal coil. T2-weighted images (TR/TE, 2000-2368/90) followed by diffusion-weighted images (TR/TE, 2500/69; b values, 0, 100, 300, 500, and 800 s/mm(2)) were acquired. An expert observer drew regions of interest around a histologically confirmed tumor on ADC maps by referring to the T2-weighted images. Pixel-by-pixel ADCs were calculated with a monoexponential fit of data from b values of 100-800 s/mm(2), and ADC histograms were obtained from the entire tumor volume. An independent samples Student t test was used to compare differences in ADC percentile values, skew, and kurtosis between squamous cell carcinoma and adenocarcinoma, well or moderately differentiated and poorly differentiated tumors, and absence and presence of lymphovascular space invasion. RESULTS There was no statistically significant difference in ADC percentiles between squamous cell carcinoma and adenocarcinoma, but the median was significantly higher in well or moderately differentiated tumors (50th percentile, 1113 ± 177 × 10(-6) mm(2)/s) compared with poorly differentiated tumors (50th percentile, 996 ± 184 × 10(-6) mm(2)/s) (p = 0.049). Histogram skew was significantly less positive for adenocarcinoma compared with squamous cell carcinoma (p = 0.016) but did not differ between tumor grades. There was no significant difference between any parameter with regard to lymphovascular space invasion. CONCLUSION Median ADC is lower in poorly compared with well or moderately differentiated tumors, while lower histogram-positive skew in adenocarcinoma compared with squamous cell carcinoma is likely to reflect the glandular content of adenocarcinoma.

Evaluation of magnetic resonance diffusion and spectroscopy measurements as predictive biomarkers in stage 1 cervical cancer

OBJECTIVE To establish whether ADC and total choline were significantly different between cervical tumors with different histological characteristics (type, degree of differentiation, presence or absence of lymphovascular invasion, lymph-node involvement) in order to establish their role as predictive biomarkers. METHODS 62 patients with stage 1 cervical cancer were scanned at 1.5 T. T2-weighted imaging (TR/TE=4500/80 ms), to identify tumor and normal cervix, was followed by diffusion-weighted imaging (TR/TE=2500/69 ms; 5 b-values 0, 100, 300, 500 and 800 s/mm(2)) and MR spectroscopic imaging (15 mm slice, 7.5 mm in-plane resolution, TR=888 ms). Regions of interest in normal cervix and tumor were drawn on apparent diffusion coefficient (ADC) maps by an expert observer with reference to the T2-weighted images. ADCs were calculated using a monoexponential fit of data from all b-values. MR spectra in voxels designated as tumor (>30% tumor) or non-tumor were quantified using LCModel and referenced to tissue water. RESULTS There was a statistically significant difference between the ADC of tumor regions (1117+/-183x10(-6) mm(2)/s) and of selected normal regions (1724+/-198x10(-6) mm(2)/s; p<0.001), and between tumors that were well/moderately differentiated (1196+/-181x10(-6) mm(2)/s) compared with those that were poorly differentiated (1038+/-153x10(-6) mm(2)/s; p=0.016). There was no significant difference between the ADCs of the tumors when separated by other characteristics (tumor type, lymphovascular invasion, lymph-node metastases), or between measured total choline in any of the groups. CONCLUSION ADCs are lower in cancer compared to normal cervical tissue, with degree of tumor differentiation contributing to this difference.

Diffusion-weighted magnetic resonance imaging for monitoring prostate cancer progression in patients managed by active surveillance

OBJECTIVES We studied patients managed by active surveillance to determine whether there was a difference over time in apparent diffusion coefficients (ADCs) derived from diffusion-weighted MRI in those who progressed to radical treatment (progressors, n = 17) compared with those who did not (non-progressors, n = 33). METHODS 50 consecutive patients (Stage T1/2a, Gleason grade ≤ 3+4, prostate-specific antigen (PSA) <15 ng ml⁻¹, <50% cores positive) were imaged endorectally (baseline and 1-3 years follow-up) with T₂ weighted (T₂W) and echo-planar diffusion-weighted MRI sequences. Regions of interest drawn on ADC maps with reference to the T₂W images yielded ADC(all) (b = 0-800), ADC(fast) (b = 0-300) and ADC(slow) (b = 300-800) for whole prostate (minus tumour) and tumour (low signal-intensity peripheral zone lesion in biopsy-positive octant). RESULTS Tumour and whole prostate ADC(all) and ADC(fast) were significantly reduced over time in progressors (p = 0.03 and 0.03 for tumours, respectively; p = 0.02 and 0.007 for the whole prostate, respectively). There were no significant changes in ADC over time in non-progressors. A 10% reduction in tumour ADC(all) indicated progression with a 93% sensitivity and 40% specificity (A(z) of receiver operating characteristic (ROC) curve = 0.68). Percentage reductions in whole prostate ADC(all), ADC(fast) and ADC(slow) were also significantly greater in progressors than in non-progressors (p = 0.01, 0.03 and 0.008, respectively). CONCLUSION This pilot study shows that DW-MRI has potential for monitoring patients with early prostate cancer who opt for active surveillance.

Diffusion-weighted Imaging of Peritoneal Disease for Noninvasive Staging of Advanced Ovarian Cancer

Cross-sectional imaging of peritoneal carcinomatosis in patients with advanced ovarian cancer is important for appropriate management but can be compromised by the small size of cancer implants and the complexity of anatomic relationships. Diffusion-weighted imaging is a functional magnetic resonance (MR) imaging technique that exploits the restricted water mobility within hypercellular tumors to increase the contrast between these lesions and surrounding tissue. Its use improves the detection and delineation of peritoneal implants at both initial staging and follow-up. Moreover, diffusion-weighted imaging provides quantitative information about tissue cellularity that may be used to distinguish viable tumors from treatment-related changes. These data allow calculation of apparent diffusion coefficient (ADC) values, which, when considered in conjunction with biochemical and morphologic parameters, are helpful for assessing the effectiveness of treatment. The value of diffusion-weighted images is maximized when they are interpreted in comparison with anatomic MR images to avoid diagnostic pitfalls arising from normal hypercellular structures and neoplasms with low cellularity. When incorporating diffusion-weighted imaging into abdominal and pelvic MR studies, it is important to be aware of the strengths and limitations of the technique. Competence in data display methods and ADC calculations also helps improve the accuracy of image interpretation and may aid in the management of patients with advanced ovarian cancer.