Validation of T2- and diffusion-weighted magnetic resonance imaging for mapping intra-prostatic tumour prior to focal boost dose-escalation using intensity-modulated radiotherapy (IMRT).

BACKGROUND AND PURPOSE: To assess the diagnostic accuracy and inter-observer agreement of T2-weighted (T2W) and diffusion-weighted (DW) magnetic resonance imaging (MRI) for mapping intra-prostatic tumour lesions (IPLs) for the purpose of focal dose-escalation in prostate cancer radiotherapy. MATERIALS AND METHODS: Twenty-six men selected for radical treatment with radiotherapy were recruited prospectively and underwent pre-treatment T2W+DW-MRI and 5 mm spaced transperineal template-guided mapping prostate biopsies (TTMPB). A 'traffic-light' system was used to score both data sets. Radiologically suspicious lesions measuring ≥0.5 cm3 were classified as red; suspicious lesions 0.2-0.5 cm3 or larger lesions equivocal for tumour were classified as amber. The histopathology assessment combined pathological grade and tumour length on biopsy (red = ≥4 mm primary Gleason grade 4/5 or ≥6 mm primary Gleason grade 3). Two radiologists assessed the MRI data and inter-observer agreement was measured with Cohens' Kappa co-efficient. RESULTS: Twenty-five of 26 men had red image-defined IPLs by both readers, 24 had red pathology-defined lesions. There was a good correlation between lesions ≥0.5 cm3 classified "red" on imaging and "red" histopathology in biopsies (Reader 1: r = 0.61, p < 0.0001, Reader 2: r = 0.44, p = 0.03). Diagnostic accuracy for both readers for red image-defined lesions was sensitivity 85-86%, specificity 93-98%, positive predictive value (PPV) 79-92% and negative predictive value (NPV) 96%. Inter-observer agreement was good (Cohen's Kappa 0.61). CONCLUSIONS: MRI is accurate for mapping clinically significant prostate cancer; diffusion-restricted lesions ≥0.5 cm3 can be confidently identified for radiation dose boosting.

Multivariate modelling of prostate cancer combining magnetic resonance derived T2, diffusion, dynamic contrast-enhanced and spectroscopic parameters.

OBJECTIVES: The objectives are determine the optimal combination of MR parameters for discriminating tumour within the prostate using linear discriminant analysis (LDA) and to compare model accuracy with that of an experienced radiologist. METHODS: Multiparameter MRIs in 24 patients before prostatectomy were acquired. Tumour outlines from whole-mount histology, T2-defined peripheral zone (PZ), and central gland (CG) were superimposed onto slice-matched parametric maps. T2, Apparent Diffusion Coefficient, initial area under the gadolinium curve, vascular parameters (K(trans),Kep,Ve), and (choline+polyamines+creatine)/citrate were compared between tumour and non-tumour tissues. Receiver operating characteristic (ROC) curves determined sensitivity and specificity at spectroscopic voxel resolution and per lesion, and LDA determined the optimal multiparametric model for identifying tumours. Accuracy was compared with an expert observer. RESULTS: Tumours were significantly different from PZ and CG for all parameters (all p < 0.001). Area under the ROC curve for discriminating tumour from non-tumour was significantly greater (p < 0.001) for the multiparametric model than for individual parameters; at 90 % specificity, sensitivity was 41 % (MRSI voxel resolution) and 59 % per lesion. At this specificity, an expert observer achieved 28 % and 49 % sensitivity, respectively. CONCLUSION: The model was more accurate when parameters from all techniques were included and performed better than an expert observer evaluating these data. KEY POINTS: • The combined model increases diagnostic accuracy in prostate cancer compared with individual parameters • The optimal combined model includes parameters from diffusion, spectroscopy, perfusion, and anatominal MRI • The computed model improves tumour detection compared to an expert viewing parametric maps.

Effect on therapeutic ratio of planning a boosted radiotherapy dose to the dominant intraprostatic tumour lesion within the prostate based on multifunctional MR parameters.

OBJECTIVE: To demonstrate the feasibility of an 8-Gy focal radiation boost to a dominant intraprostatic lesion (DIL), identified using multiparametric MRI (mpMRI), and to assess the potential outcome compared with a uniform 74-Gy prostate dose. METHODS: The DIL location was predicted in 23 patients using a histopathologically verified model combining diffusion-weighted imaging, dynamic contrast-enhanced imaging, T2 maps and three-dimensional MR spectroscopic imaging. The DIL defined prior to neoadjuvant hormone downregulation was firstly registered to MRI-acquired post-hormone therapy and subsequently to CT radiotherapy scans. Intensity-modulated radiotherapy (IMRT) treatment was planned for an 8-Gy focal boost with 74-Gy dose to the remaining prostate. Areas under the dose-volume histograms (DVHs) for prostate, bladder and rectum, the tumour control probability (TCP) and normal tissue complication probabilities (NTCPs) were compared with those of the uniform 74-Gy IMRT plan. RESULTS: Deliverable IMRT plans were feasible for all patients with identifiable DILs (20/23). Areas under the DVHs were increased for the prostate (75.1 ± 0.6 vs 72.7 ± 0.3 Gy; p < 0.001) and decreased for the rectum (38.2 ± 2.5 vs 43.5 ± 2.5 Gy; p < 0.001) and the bladder (29.1 ± 9.0 vs 36.9 ± 9.3 Gy; p < 0.001) for the boosted plan. The prostate TCP was increased (80.1 ± 1.3 vs 75.3 ± 0.9 Gy; p < 0.001) and rectal NTCP lowered (3.84 ± 3.65 vs 9.70 ± 5.68 Gy; p = 0.04) in the boosted plan. The bladder NTCP was negligible for both plans. CONCLUSION: Delivery of a focal boost to an mpMRI-defined DIL is feasible, and significant increases in TCP and therapeutic ratio were found. ADVANCES IN KNOWLEDGE: The delivery of a focal boost to an mpMRI-defined DIL demonstrates statistically significant increases in TCP and therapeutic ratio.

Relationship between T2 relaxation and apparent diffusion coefficient in malignant and non-malignant prostate regions and the effect of peripheral zone fractional volume.

OBJECTIVE: To establish whether T2 relaxation and apparent diffusion coefficient (ADC) in normal prostate and tumour are related and to investigate the effects of glandular compression from an enlarged transition zone (TZ) on peripheral zone (PZ) T2 and ADC by correlating them with the peripheral zone fractional volume (PZFV). METHODS: 48 consecutive patients prospectively underwent multiecho T2 weighted (T2W) (echo times 20, 40, 60, 80, 100 ms) and diffusion-weighted (b=0, 100, 300, 500, 800 s mm(-2)) endorectal MRI. In 43 evaluable patients, single slice whole PZ, TZ and tumour (focal hypointense signal on T2W images in a biopsy-positive octant) regions of interest were transferred to T2 and ADC maps by slice matching. T2 and ADC values were correlated, and PZ values were correlated with PZFV. RESULTS: T2 and ADC values were significantly different among groups [T2 mean±standard deviation (SD) PZ, 149±49 ms; TZ, 125±26 ms; tumour, 97±23 ms; PZ vs TZ, p=0.002; PZ vs tumour, p<0.0001; TZ vs tumour, p<0.0001; ADC×10(-6) mm(2) s(-1) mean±SD PZ, 1680±215; TZ, 1478±139; tumour, 1030±205; p<0.0001]. Significant positive correlations existed between T2 and ADC for PZ, TZ, PZ and TZ together, but not for tumour (r=0.515, p<0.0001; r=0.300, p=0.03; r=0.526, p<0.0001; and r=0.239, p=0.32, respectively). No significant correlation existed between PZFV and PZ T2 (r=0.10, p=0.5) or ADC (r=0.03, p=0.8). CONCLUSION: The correlation between T2 and ADC that exists in normal prostate is absent in tumour. PZ compression by an enlarged TZ does not alter PZ T2 or ADC to affect tumour-PZ contrast. ADVANCES IN KNOWLEDGE: Microstructural features of tumours alter diffusivity independently of their effects on T2 relaxation.

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 the prostate and rectal wall: comparison of biexponential and monoexponential modelled diffusion and associated perfusion coefficients.

This study compares parameters from monoexponential and biexponential modelling of diffusion-weighted imaging of normal and malignant prostate tissue and normal rectal wall tissues. Fifty men with Stage Ic prostate cancer were studied using endorectal T(2)-weighted imaging and diffusion-weighted imaging with 11 diffusion-sensitive values (b-values = 0, 1, 2, 4, 10, 20, 50, 100, 200, 400, 800 s/mm(2)). Regions of interest were drawn within non-malignant central gland and peripheral zone, malignant prostate tissue and normal rectal wall tissue. Both a monoexponential and biexponential model was fitted over various b-value ranges, giving an apparent diffusion coefficient (ADC) from the monoexponential model and a diffusion coefficient, perfusion coefficient and perfusion fraction from the biexponential model. In all tissues, over the full range of b-values, the ADC from the monoexponential model was significantly higher than the corresponding diffusion coefficient from the biexponential model. As the minimum b-value increased, the ADC decreased and was equal to the diffusion coefficient for some b-value ranges. The biexponential model best described the data when low b-values were included, suggesting that there is a fast perfusion component. Neither model could distinguish between benign prostate tissues on the basis of diffusion coefficients, but the rectal wall tissue and malignant prostate tissue had significantly lower diffusion coefficients than normal prostate tissues. Perfusion coefficients and fractions were highly variable within the population, so their clinical utility may be limited, but removal of this variable perfusion component from reported diffusion coefficients is important when attributing clinical differences to diffusion within tissues.

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.

EU Directive 2004/40: field measurements of a 1.5 T clinical MR scanner.

The European Union (EU) Physical Agents (EMF) Directive [1] must be incorporated into UK law in 2008. The directive, which applies to employees working in MRI, sets legal exposure limits for two of the three types of EMF exposure employed in MRI; time-varying gradient fields and radiofrequency (RF) fields. Limits on the static field are currently not included but may be added at a later date. Conservative action values have been set for all three types of exposure including the static field. The absolute exposure limits will exclude staff from the scanner bore and adjacent areas during scanning, impacting on many clinical activities such as anaesthetic monitoring during sedated scans, paediatric scanning and interventional MRI. When the legislation comes into force, NHS Trusts, scanner companies and academic institutions will be required to show compliance with the law. We present results of initial measurements performed on a 1.5 T clinical MRI scanner. For the static field, the proposed action value is exceeded at 40 cm from the scanner bore and would be exceeded when positioning a patient for scanning. For the RF field, the action values were only exceeded within the bore at distances of 40 cm from the scanner ends during a very RF intensive sequence; MRI employees are unlikely to be in the bore during an acquisition. For the time-varying gradient fields the action values were exceeded 52 cm out from the mouth of the bore during two clinical sequences, and estimated current densities show the exposure limit to be exceeded at 40 cm for frequencies above 333 Hz. Limiting employees to distances greater than these from the scanner during acquisition will have a severe impact on the future use and development of MRI.