Publications

Objectives To measure apparent diffusion coefficient (ADC) values in patients with active myeloma and remission and to determine whether changes differ in those responding/progressing on treatment. The relationship between changes in marrow fat and ADC was also explored. Methods 20 patients were recruited. T(1 )weighted, T(2) weighted, short tau inversion-recovery, diffusion-weighted and two-point Dixon MRI of the lumbar spine and pelvis were performed at baseline, 4-6 weeks and 20 weeks. Results ADC values of active disease (mean 761.2±255×10(-6) mm(2) s(-1)) were significantly higher (p=0.047) than marrow in remission (mean 601.8±459×10(-6) mm(2) s(-1)). Changes in ADC in responders showed a significant increase at 4-6 weeks (p=0.005) but no significant change between baseline and 20 weeks (p=0.733). ADCs in progressing and stable patients did not change significantly between either time point. Pearson's correlation coefficient between change in fat fraction and change in the number of pixels with an ADC of ≤655×10(-6) mm(2) s(-1) was 0.924, indicating a significant correlation (p<0.001). Conclusion ADC values in active myeloma are significantly higher than marrow in remission, indicating the potential for diffusion-weighted MRI to quantify the transition from active disease to remission and vice versa. This study confirms significant changes in ADC in patients responding to treatment and indirect evidence from two-point Dixon MRI suggests that these changes are influenced by changes in marrow fat. Advances in knowledge ADC of active myeloma is significantly higher than marrow in remission; the direction of ADC changes on treatment is dependent on the timing of measurements and is influenced by changes in marrow fat.

Purpose: To assess baseline reproducibility and compare performance of dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging versus DCE computed tomographic (CT) measures of early vascular response in the same patients treated with cediranib (30 or 45 mg daily). Materials and Methods: After institutional review board approval, written informed consent was obtained from 29 patients with advanced solid tumors who had lesions 3 cm or larger and in whom simultaneous imaging of an adjacent artery was possible. Two baseline DCE MR acquisitions and two baseline DCE CT acquisitions 7 days or fewer apart (within 14 days of starting treatment) and two posttreatment acquisitions with each modality at day 7 and 28 (±3 days) were obtained. Nonmodeled and modeled parameters were derived (measured arterial input function [AIF] for CT, population-based AIF for MR imaging; temporal sampling rate of 0.5 second for CT, 3-6 seconds for MR imaging). Baseline variability was assessed by using intra- and intersubject analysis of variance and Bland-Altman analysis; a paired t test assessed change from baseline to after treatment. Results: The most reproducible parameters were DCE MR imaging enhancement fraction (baseline intrapatient coefficient of variation [CV] = 8.6%), volume transfer constant (CV = 13.9%), and integrated area under the contrast agent uptake curve at 60 seconds (CV = 15.5%) and DCE CT positive enhancement integral (CV = 16.0%). Blood plasma volume was highly variable and the only parameter with CV greater than 30%. Average reductions (percentage change) from baseline were consistently observed for all DCE MR imaging and DCE CT parameters at day 7 and 28 for both starting-dose groups (45 and 30 mg), except for DCE CT mean transit time. Percentage change from baseline for parameters reflecting blood flow and permeability were comparable, and reductions from baseline at day 7 were maintained at day 28. Conclusion: DCE MR imaging and DCE CT can depict vascular response to antiangiogenic agents with response evident at day 7. Improved reproducibility with MR imaging favors its use in trials with small patient numbers. © RSNA, 2012 Clinical trial registration no. NCT00748891 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112565/-/DC1.

The objectives of our study were to establish the apparent diffusion coefficients (ADCs) of tumor and nontumor irradiated tissues in patients with suspected postradiation recurrence of prostate cancer and to determine the sensitivity and specificity of a combination of T2-weighted and diffusion-weighted imaging (DWI) for detecting local recurrence.

Key issues in early clinical trials of targeted agents include the determination of target inhibition, rational patient selection based on pre-treatment tumour characteristics, and assessment of tumour response in the absence of actual shrinkage. There is accumulating evidence that functional imaging using advanced techniques such as dynamic contrast enhanced (DCE)-magnetic resonance imaging (MRI), DCE-computerised tomography (CT) and DCE-ultrasound, diffusion weighted-MRI, magnetic resonance spectroscopy and positron emission tomography-CT using various labelled radioactive tracers has the potential to address all three. This article reviews this evidence with examples from trials using targeted agents with established clinical efficacy and summarises the clinical utility of the various techniques. We therefore recommend that input from specialist radiologists is sought at the early stages of trial design, in order to ensure that functional imaging is incorporated appropriately for the agent under study. There is an urgent need to strengthen the evidence base for these techniques as they evolve, and to ensure standardisation of the methodology.

This study aimed to characterize changes in lipid saturation using magnetic resonance spectroscopy of sensitive (HeLa) and resistant (C33A; Me180) cervical cancer cell lines following exposure to paclitaxel to explore lipid profiles as biomarkers of drug resistance. Spectra were acquired at 11.74 T. Flow cytometry, electron, and confocal microscopy assessed cellular morphology. Western blots assessed cytoplasmic phospholipase A(2) , fatty acid synthase, and acyl-CoA synthetase1 expression. After 24 h of paclitaxel exposure, >60% of cells showed mitotic arrest. At 48 h, HeLa cells showed apoptosis while C33A/Me180 cells showed normal morphology indicating resistance. MR-visible lipids increased significantly in all lines at 24 h with further increases at 48 h; resistant lines showed smaller increases than HeLa. Cytoplasmic phospholipase A(2) and fatty acid synthase levels were unchanged at 24 h and dropped at 48 h in HeLa; acyl-CoA synthetase1 was higher in Me180/C33A than in HeLa controls but did not increase significantly. The percentage of cells displaying lipid droplets increased significantly at 24 and 48 h in all lines; droplet size increased only in HeLa cells. Droplet number was >3-4× greater in apoptotic compared with mitotic-arrested cells. Apoptotic cells accumulate unsaturated fatty acids in large (relative to control) droplets; resistant lines accumulated smaller droplets with less triglycerides.

To prospectively evaluate apparent diffusion coefficient (ADC) histograms in the prediction of chemotherapy response in patients with metastatic ovarian or primary peritoneal cancer.

To evaluate the effects of previous cone biopsy and lesion size on detectability of stage 1a/1b cervical cancer using endovaginal T2- and diffusion-weighted magnetic resonance imaging.

The purpose of our study was to investigate whether fast and slow components of the apparent diffusion coefficient (ADC) from diffusion-weighted MR images could predict 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 T-2 weighted (T2W) and echo-planar diffusion-weighted MRI sequences. Regions of interest drawn on ADC maps with reference to the T2W images yielded AD(Call) (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.

The hepatocyte growth factor/c-MET axis is implicated in tumor cell proliferation, survival, and angiogenesis. ARQ 197 is an oral, selective, non-adenosine triphosphate competitive c-MET inhibitor. A phase I trial of ARQ 197 was conducted to assess safety, tolerability, and target inhibition, including intratumoral c-MET signaling, apoptosis, and angiogenesis.

ABSTRACT: Functional magnetic resonance (MR) encompasses a spectrum of techniques that depict physiological and molecular processes before morphological changes are visible on conventional imaging. As understanding of the pathophysiological and biomolecular processes involved in breast malignancies evolves, newer functional MR techniques can be employed that define early predictive and surrogate biomarkers for monitoring response to chemotherapy. Neoadjuvant chemotherapy is increasingly used in women with primary breast malignancies to down-stage the tumour and enable successful breast conservation surgery. It also plays a role in the treatment of undetected micrometastases. Cardinal physiological features of tumours that occur as a result of interactions between cancer cells, stromal cells and secreted factors and cytokines and how they change with treatment provide the opportunity to detect changes in the tumour microenvironment prior to any morphological change. Through sequential imaging, tumour response can be assessed and non-responders can be identified early to enable alternative therapies to be considered. This review summarises the functional magnetic resonance biomarkers of response in patients with breast cancer that are currently available and under development. We describe the current state of each biomarker and explore their potential clinical uses and limitations in assessing treatment response. With the aid of selected interesting cases, biomarkers related to dynamic contrast-enhanced MRI, diffusion-weighted MRI, T2*/BOLD and MR spectroscopy are described and illustrated. The potential of newer approaches, such as MR elastography, are also reviewed.

Functional MRI techniques are increasingly being used for prostate cancer imaging, but their implementation differs markedly among institutions. A set of recommendations has now been published in an attempt to standardize protocols; however, the guidelines were devised without the use of evidence-based data, and require further scrutiny.

OBJECTIVES: To establish normal bone marrow values of apparent diffusion coefficient (ADC) over an age range, compare them with metastatic and myelomatous involvement, to establish reproducibility and to optimise b values. METHODS: The ADCs of bone marrow in 7 volunteers (mean age 29.7 years), 34 volunteers (mean age 63.3 years) and 43 patients with metastatic and myelomatous involvement (mean age 65.5 years) were measured. In 9 volunteers diffusion weighted MRI was repeated within 7 days. b values were derived to optimise contrast between normal and pathological marrow. RESULTS: The mean ADC of bone marrow in younger volunteers was significantly higher than that of older volunteers. The coefficient of reproducibility was 14.8%. The ADC mean of metastatic and myeloma bone disease was [Formula: see text]. An ADC threshold of 655 × 10(-6) mm(2)s(-1) separated normal and abnormal marrow with a sensitivity and specificity of 90% and 93% respectively. Contrast between normal and abnormal marrow was optimal at b = 1389 smm(-2). CONCLUSION: The reproducibility of ADC measurements in bone is equivalent to published data for soft tissue with a high sensitivity and specificity for separating abnormal from age matched normal bone marrow. A b value of around 1,400 smm(-2) is optimal for imaging bone marrow.

Pharmacokinetic parameters from dynamic contrast-enhanced MRI (DCE-MRI) were used to assess the perfusion effects due to treatment response using a tyrosine kinase inhibitor. A Bayesian hierarchical model (BHM) is proposed, as an alternative to voxel-wise estimation procedures, to test for a treatment effect while explicitly modeling known sources of variability.Nine subjects from a randomized, blinded, placebo-controlled, multicenter, phase II study of lapatinib were examined before and after treatment. Kinetic parameters were estimated, with an extended compartmental model and subject-specific arterial input function, on a voxel-by-voxel basis.The group treated with lapatinib had a decrease in median K (trans) of 0.17min(-1), when averaged across all voxels in the tumor ROIs, compared with no change in the placebo group based on nonlinear regression. A hypothesis test of equality between pre- and posttreatment K (trans) could not be rejected against a one-sided alternative (P = 0.09). Equality between median K (trans) in placebo and lapatinib groups posttreatment could also not be rejected using the BHM (P = 0.32). Across all scans acquired in the study, estimates of K (trans) at one site were greater on average than those at the other site by including a site effect in the BHM. The inter-voxel variability is of similar order (within 15%) when compared to the inter-patient variability.Though the study contained a small number of subjects and no significant difference was found, the Bayesian hierarchical model provided estimates of variability from known sources in the study and confidence intervals for all estimated parameters. We believe the BHM provides a straightforward and thorough interrogation of the imaging data at the level of voxels, patients or sites in this multicenter clinical study.

There has been considerable progress in the imaging of cervical cancer over the last 5 years. In countries with access to cross-sectional imaging resources, technical advances have enabled a range of imaging techniques to become increasingly employed and established in the detection, staging and treatment planning of cervical cancer and for identifying disease recurrence. This review highlights these developments and summarizes recent significant articles.

Purpose: To prospectively evaluate apparent diffusion coefficient (ADC) histograms in predicting chemotherapy response in patients with metastatic ovarian or primary peritoneal cancer. Materials and Methods: Research ethics committee approval and patients’ written informed consent were obtained. Diffusion-weighted (DW) MR imaging was performed through abdomen and pelvis before and after one and three cycles of chemotherapy in 42 women (mean age, 63.0 years ± 11.4) with newly diagnosed or recurrent disease. Reproducibility and intra- and inter-observer agreement of ADC calculations were assessed. Per-patient weighted ADC histograms were generated at each timepoint from pixel ADCs from ≤5 target lesions. Mean ADC, percentiles (C10, C25, C50, C75, C90), skew, kurtosis and their change were analyzed according to histological grade, primary vs. recurrent disease status and response, determined on integrated biochemical and morphological criteria, with a linear mixed model. Areas under receiver operating characteristics curves (AUCs) for combinations of parameters were calculated with linear discriminant analysis. Results: Coefficients of variation for repeat measurements and within and between observers were 4.8%, 11.4% and 13.7% respectively. Grade and disease status did not significantly affect histogram parameters. Pre-treatment ADCs were not predictive of response. In responders all ADCs increased after the 1st and 3rd cycle (P < .001), while skew and kurtosis decreased after the 3rd (P < .001 and P = .006 respectively); however, in non-responders no parameter changed significantly. Percentage C25 change performed better in identifying response (AUC = .82 and .83 after 1st and 3rd cycle respectively), whereas combination of parameters did not improve accuracy. Conclusion: An early increase of ADC values and later decrease of skew and kurtosis characterize chemotherapy response. Quantitative DW-MR imaging can aid early monitoring of treatment efficacy in patients with advanced ovarian cancer.

The Gynaecological Cancer InterGroup conducts collaborative trials in gynecologic cancer and also aims to develop standards that can be used to strengthen all aspects of study methodology. There is an urgent need to develop more refined imaging end points that can be used as early treatment response biomarkers in ovarian cancer. Therefore, the Gynaecological Cancer InterGroup commissioned an expert position paper on the role of functional imaging as an end point in clinical trials in ovarian cancer. In this position paper, we state the limitation of current anatomical imaging methods used in clinical trials, highlight the potential of functional imaging, and provide key recommendations on the use of functional imaging as an end point in ovarian cancer clinical trials.

The aim of this work was to investigate the effect of experimental conditions on the visibility of polyamines. In solution the chemical shift of the three groups of peaks (at approximately 1.8, 2.1 and 3.1 ppm) were found to be pH dependent. Relaxation times in aqueous solution at pH 7.0, 298 K and 11.74 T were measured to be: putrescine (T(1) = 2.49 s, T(2) = 2.07 s), spermidine (T(1) = 1.27 s, T(2) = 1.05 s) and spermine (T(1) = 1.02 s, T(2) = 0.82 s). Simple spin-echo sequences could not be used to measure T(2) as the spins also experience phase evolution from homonuclear coupling which imposes a modulation on the T(2) decay curve. This modulation is eliminated by using CPMG sequences with an echo spacing of <500 micros. Relaxation times for spermine in solution in presence of metal ions and protein showed that metal ions had little effect on T(2); however, addition of 15 mg/ml bovine serum albumin reduced T(2) of spermine (0.41 s at 298 K and 0.19 s at 277 K) but was not as short as the T(2) of the polyamine peak in prostatic tissue (0.03 s at 277 K). The MR visibility of polyamines in prostate cell extracts, PC-3 xenograft (intact as well as extracted) and intact human prostatic tissues were investigated. Polyamines were not detected in methanol/chloroform extracts, but were visible in perchloric acid extracts of prostate tumour cells. No polyamines were detected in the HR MAS spectra of three samples of whole PC-3 xenograft tissue studied. In summary, the chemical shift of polyamine species is pH dependent, while protein binding causes peak broadening and reduction in T(2). Perchloric acid extraction improves visibility of intracellular polyamines, but whole tissue polyamines are not seen in xenografts without epithelial/ ductal structure.

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.

The purpose of this study was to implement a diffusion-weighted sequence for visualisation of mobile lipid resonances (MLR) using high resolution magic angle spinning (HR-MAS) (1)H MRS and to evaluate its use in establishing differences between tissues from patients with cervical carcinoma that contain cancer from those that do not. A stimulated echo sequence with bipolar gradients was modified to allow T(1) and T(2) measurements and optimised by recording signal loss in HR-MAS spectra as a function of gradient strength in model lipids and tissues. Diffusion coefficients, T(1) and apparent T(2) relaxation times were measured in model lipid systems. MLR profiles were characterised in relation to T(1) and apparent T(2) relaxation in human cervical cancer tissue samples. Diffusion-weighted (DW) spectra of cervical biopsies were quantified and peak areas analysed using linear discriminant analysis (LDA). The optimised sequence reduced spectral overlap by suppressing signals originating from low molecular weight metabolites and non-lipid contributions. Significantly improved MLR visualisation allowed visualisation of peaks at 0.9, 1.3, 1.6, 2.0, 2.3, 2.8, 4.3 and 5.3 ppm. MLR analysis of DW spectra showed at least six peaks arising from saturated and unsaturated lipids and those arising from triglycerides. Significant differences in samples containing histologically confirmed cancer were seen for peaks at 0.9 (p < 0.006), 1.3 (p < 0.04), 2.0 (p < 0.03), 2.8 (p < 0.003) and 4.3 ppm (p < 0.0002). LDA analysis of MLR peaks from DW spectra almost completely separated two clusters of cervical biopsies (cancer, 'no-cancer'), reflecting underlying differences in MLR composition. Generated Receiver Operating Characteristic (ROC) curves and calculated area under the curve (0.962) validated high sensitivity and specificity of the technique. Diffusion-weighting of HR-MAS spectroscopic sequences is a useful method for characterising MLR in cancer tissues and displays an accumulation of lipids arising during tumourigenesis and an increase in the unsaturated lipid and triglyceride peaks with respect to saturated MLR.

Diffusion Weighted Magnetic Resonance Imaging (DW-MRI) combined with conventional MRI can provide a whole body assessment of metastatic bone disease, improved lesion detection compared to other imaging techniques and a direct quantitative assessment of treatment response. In bone marrow, the presence of fat and bone trabeculae and their changing contributions with disease progression and response to treatment present unique challenges for data acquisition and image interpretation. This article discusses these challenges and reviews the potential of DW-MRI to provide a biomarker of response in metastatic bone disease.

Peritoneal metastases are often the first presentation of ovarian malignancy. Evaluating the extent of disease critically determines tumor resectability and can also predict outcome. Standard CT, however, frequently fails to identify small sites of peritoneal spread. Moreover, it does not provide a quantitative index of disease response to cytotoxic therapy as it relies on macroscopic morphological changes in tumor volume, and does not reflect preceding molecular events in the microenvironment of the tumor. We describe the emerging role of functional imaging techniques, such as radioimmunoscintigraphy, PET/CT, diffusion-weighted MRI, dynamic contrast-enhanced MRI, and magnetic resonance spectroscopy in staging ovarian cancer and assessing treatment response. The combination of functional information with conventional anatomical visualization holds promise to accurately characterize peritoneal disease, and provides noninvasive biomarkers of therapeutic performance and patient prognosis.

To compare geometric distortion, signal-to-noise ratio (SNR), apparent diffusion coefficient (ADC), efficacy of fat suppression and presence of artefact between monopolar (Stejskal and Tanner) and bipolar (twice-refocused, eddy-current-compensating) diffusion-weighted imaging (DWI) sequences in the abdomen and pelvis.

This study correlates apparent diffusion coefficients (ADCs) from Diffusion-weighted Imaging (DWI) in primary ovarian tumours and their omental metastases following neoadjuvant chemotherapy with epithelial and stromal densities in order to relate them to histological composition. Eight patients underwent DWI at 1.5 T with four b-values (0, 600, 900, and 1,050 s/mm(2))at baseline and after one and three cycles of platinum-based chemotherapy. Mean ADCs were calculated at each timepoint from solid tumour at ovarian and omental sites. Specimens from 15 corresponding lesions (8 ovarian, 7 omental), obtained at interval debulking surgery, were stained immunohistochemically to quantify epithelial and stromal components. End-of-treatment ADC was correlated with epithelial and stromal densities. Longitudinal changes in ADC with treatment were compared between primary and metastatic lesions using parametric tests. No baseline differences in ADC between primary and metastatic sites were seen. Mean ADC increased significantly from baseline after both first and third cycle (P < 0.001) in both ovarian and omental lesions. ADC and total epithelial plus stromal density (lesion cellularity) were negatively correlated in ovarian lesions (r= -0.79, P=0.02) but not in omental metastases or when both sites were considered together. However, ADC and epithelial density were negatively correlated in ovarian (r=- 0.78, P=0.02) and omental lesions (r=-0.75, P=0.04) and when both sites were considered together (r=-0.77, P< 0.001). There was no significant correlation between ADC and stromal density. Thus ADC reflects mainly epithelial content in advanced ovarian cancer and is not solely a function of lesion cellularity.

Ultra Short TE MRI allows signal to be detected from tissues with a very short T2.The aims of this study were to optimize a 2D UTE MRI sequence for imaging and quantification of sclerotic bone metastases, establish T2* values of sclerotic components and investigate the feasibility of using the method to assess changes in T2* of sclerotic metastases and their relation to attenuation values in patients on treatment.

The aim of this study was to determine the metabolic changes in the transition from pre-invasive to invasive cervical cancer using high-resolution magic angle spinning (HR-MAS) MRS. Biopsy specimens were obtained from women with histologically normal cervix (n = 5), cervical intraepithelial neoplasia (CIN; mild, n = 5; moderate/severe, n = 40), and invasive cancer (n = 23). (1)H HR-MAS MRS data were acquired using a Bruker Avance 11.74 T spectrometer (Carr-Purcell-Meiboom-Gill sequence; TR = 4.8 s; TE = 135 ms; 512 scans; 41 min acquisition). (31)P HR-MAS spectra were obtained from the normal subjects and cancer patients only (as acetic acid applied before tissue sampling in patients with CIN impaired spectral quality) using a (1)H-decoupled pulse-acquire sequence (TR = 2.82 s; 2048 scans; 96 min acquisition). Peak assignments were based on values reported in the literature. Peak areas were measured using the AMARES algorithm. Estimated metabolite concentrations were compared between patient diagnostic categories and tissue histology using independent samples t tests. Comparisons based on patient category at diagnosis showed significantly higher estimated concentrations of choline (P = 0.0001) and phosphocholine (P = 0.002) in tissue from patients with cancer than from patients with high-grade dyskaryosis, but no differences between non-cancer groups. Division by histology of the sample also showed increases in choline (P = 0.002) and phosphocholine (P = 0.002) in cancer compared with high-grade CIN tissue. Phosphoethanolamine was increased in cancer compared with normal tissue (P = 0.0001). Estimated concentrations of alanine (P = 0.01) and creatine (P = 0.008) were significantly reduced in normal tissue from cancer patients compared with normal tissue from non-cancer patients. The estimated concentration of choline was significantly increased in CIN tissue from cancer patients compared with CIN tissue from non-cancer patients (P = 0.0001). Estimated concentrations of choline-containing metabolites increased from pre-invasive to invasive cervical cancer. Concurrent metabolite depletion occurs in normal tissue adjacent to cancer tissue.

To investigate epithelial and stromal metabolite changes in cervical intraepithelial neoplasia (CIN) and cervical cancer in vivo and correlate findings with MR spectroscopy of tissue samples. Forty-seven women (19 with CIN, 28 with cervical cancer) underwent endovaginal MR at 1.5 T with T2-W and localised 2D MR spectroscopic imaging (PRESS, TR = 1,500 ms, TE = 135 ms). tCho, 2 ppm and -CH(2) lipid peaks were measured in epithelial (>50% epithelium, no tumour), stromal (>50% stroma, no tumour) and tumour (>30% tumour) voxels. Unsuppressed water signal from the same voxel provided a concentration reference. (1)H HR-MAS MR spectra were acquired from tissue in 37 patients (11.74 T, pulse-acquire and cpmg sequences, with water pre-saturation). Analysable data from 17 CIN and 25 cancer patients showed significant increases in tCho (p = 0.03) and 2 ppm (p = 0.007) in tumour compared with epithelial voxels from CIN patients, but not with epithelial voxels from cancer patients. No significant differences were seen in stroma from cancer compared with CIN patients. Differences in -CH(2) lipids were not significant between groups. There was no significant correlation between in vivo and ex vivo tCho or -CH(2) lipids. Estimated in vivo concentrations of tCho and 2 ppm resonances increase in tumour and adjacent epithelium in progression from CIN to cervical cancer.

There is growing interest in diffusion weighted magnetic resonance imaging (MRI) of cervical carcinoma but normal uterine appearances and effects of the oral contraceptive pill (OCP) have not been described.

Imaging bone metastases from prostate cancer presents several challenges. The lesions are usually sclerotic and appear late on the conventional X-ray. Bone scintigraphy is the mainstay of lesion detection, but is often not suitable for assessment of treatment response, particularly because of a 'flare' phenomenon after therapy. Magnetic resonance imaging is increasingly used in assessment, and newer techniques allow quantitation. In addition to (18)F-fluorodeoxyglucose ((18)FDG), newer PET isotopes are also showing promise in lesion detection and response assessment. This article reviews the available imaging modalities for evaluating prostatic bony metastases, and links them to the underlying pathological changes within bone lesions.

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.

To compare tumor bed (TB) volumes delineated using magnetic resonance imaging plus computed tomography and clips (MRCT) with those delineated using CT and clips (CT/clips) alone in postlumpectomy breast cancer patients positioned prone and to determine the value of MRCT for planning partial breast irradiation (PBI).

The purpose of this study was to compare the apparent diffusion coefficient (ADC) of benign central gland (bCG), benign peripheral zone (bPZ) and cancer using diffusion-weighted MRI and whole mount specimens. 11 patients with biopsy-proven prostate cancer underwent diffusion-weighted MRI prior to radical prostatectomy. A single-shot echo planar image technique was used with b-values of 0 s mm(-2), 300 s mm(-2), 500 s mm(-2) and 800 s mm(-2). Whole mount specimens were compared with ADC maps. Areas of cancer, bCG and bPZ were identified, and regions of interest were drawn on ADC maps. Mean ADC values were recorded for all regions of interest, and paired t-tests were performed to compare mean values. Cancer was outlined in nine patients. In two patients, the tumours were too small to correlate with images; bCG was identified in 11 patients and bPZ was identified in 10 patients. Mean ADC values for bCG, bPZ and cancer were, 1.5 x 10(-3) mm(2) s(-1) (standard error (SE) = 0.04), 1.7 x 10(-3) mm(2) s(-1) (SE = 0.1), and 1.3 x 10(-3) mm(2) s(-1) (SE = 0.09), respectively. The most significant difference between benign tissue and cancer existed at b-values of 0-300 s mm(-2) (bCG vs cancer: mean difference = 0. 29, p = 0.001, 95% confidence interval (CI) = 0.17-0.41; bPZ vs cancer: mean difference = 0.34, p = 0.003, 95% CI = 0.18-0.61). In conclusion, we have confirmed, using whole mount verification, a significant difference in the ADC between benign tissue and cancer.

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.

To compare the diagnostic accuracy of MnDPDP MR imaging and diffusion-weighted imaging (DWI), alone and in combination, for detecting colorectal liver metastases in patients with suspected metastatic disease. Thirty-three consecutive patients with suspected colorectal liver metastases underwent MR imaging. Three image sets (MnDPDP, DWI and combined MnDPDP and DWI) were reviewed independently by two observers. Lesions were scored on a five-point scale for malignancy and the areas (Az) under the receiver operating characteristic curves were calculated for each observer and image set. The sensitivity and specificity for lesion detection were calculated for each image set and compared. There were 83 metastases, 49 cysts and 1 haemangioma. Using the combined set resulted in the highest diagnostic accuracy for both observers (Az=0.94 and 0.96), with improved averaged sensitivity of lesion detection compared with the DWI set (p=0.01), and a trend towards improved sensitivity compared with the MnDPDP set (p=0.06). There was no difference in the averaged specificity using any of the three image sets (p > 0.5). Combination of MnDPDP MR imaging and DWI resulted in the highest diagnostic accuracy and can increase sensitivity without loss in specificity.

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 <= 6, prostate-specific antigen (PSA) 10 (group 1)] or intermediate/high- [n = 18, stage >= T2b and/or Gleason score >= 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. (C) 2008 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Gliomatosis peritonei is a rare complication of ovarian teratomas characterized by peritoneal implants of glial tissue. Glial tissue in such cases is usually low grade although there have been cases of malignant evolution described. There is no clear guidance as to how often and for how long these patients should be followed up. There are clear dose implications when performing multiple CT scans. We present a case of immature ovarian teratoma complicated by the development of low grade gliomatosis peritonei. The MRI appearances are presented and described, and we discuss the potential role of MRI in the follow up of such cases.

To integrate a high intensity focused ultrasound (HIFU) transducer with an MR receiver coil for endocavitary MR-guided thermal ablation of localized pelvic lesions.

The aim of this work was to determine the potential of diffusion weighted magnetic resonance imaging (DW-MRI) for identifying prostate cancer by comparing apparent diffusion coefficients (ADCs) from malignant peripheral zone (PZ) nodules with values from the non-malignant PZ and the predominantly benign central gland (CG). 33 patients with elevated prostate specific antigen (PSA) aged 52-78 years (30 patients with biopsy proven prostate cancer) underwent endorectal MRI with T2 weighted and echo planar diffusion weighting (b = 0 mm2 s(-1), 300 mm2 s(-1), 500 mm2 s(-1) and 800 mm2 s(-1)) sequences. ADCs were measured from 30 malignant PZ nodules (identified on T2 weigting and positive biopsy; median region of interest (ROI) size 41 mm2), 33 CG regions (predominantly benign nodules; median ROI size 218 mm2) and 18 non-malignant PZ regions (ipsilateral biopsies all benign; median ROI size 54.5 mm2). ADCs were (mean+/-standard deviation (SD); mm2 s(-1)): malignant PZ nodules 1.30+/-0.30x10(-3), CG 1.46+/-0.14x10(-3) and non-malignant PZ 1.71+/-0.16x10(-3). Differences between all three groups were statistically significant (p = 0.01 malignant PZ vs CG; p = 0.0001 malignant PZ vs non-malignant PZ and p = 0.0001 CG vs non-malignant PZ). Using receiver operating characteristic curves, cut-off values of 1.39x10(-3) mm2 s(-1) differentiated malignant PZ nodules from predominantly benign CG (sensitivity 60%, specificity 76%) and of 1.6x10(-3) mm2 s(-1) identified malignant from non-malignant PZ (sensitivity 86.7%, specificity 72.2%). These results suggest that DW-MRI has the potential to increase the specificity of prostate cancer detection because ADCs are significantly lower in malignant compared with non-malignant prostate tissue.

Conventional T2-weighted (T2W) imaging alone has a poor sensitivity for prostate cancer detection.

OBJECTIVE. The objective of our study was to establish the sensitivity and specificity for prostate cancer detection using a combined H-1 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 B-0 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 >= 30% 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 >= 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.

Magnetic Resonance Imaging (MRI) is the criterion standard in the assessment and staging of uterine cancer because of the high tissue contrast between glandular lining and inner and outer muscle layers of the uterine corpus and cervix on T2-weighted scans. It is also an essential tool in monitoring treatment response and in assessing disease recurrence in these patients. The key to a successful examination lies in good patient preparation, use of antiperistaltic agents, and a meticulous scanning technique. Endometrial carcinomas are the most common uterine malignancy, occurring in a primarily postmenopausal population. Dynamic contrast-enhanced scans may be required in addition to T2-weighted images to assess the presence of myometrial invasion in this age group. Cervical cancers occur in a younger population and are readily assessed with T2-weighted imaging. Use of an endovaginal receiver coil allows high spatial resolution imaging of the cervix, which is particularly useful when assessing patients for fertility-sparing procedures such as trachelectomy. Uterine sarcomas are 1% to 3% of all uterine malignancies and usually arise from a mixture of homologous and heterologous elements. Rarely, lymphoma, small cell carcinoma and metastatic deposits involve the uterus. This review summarizes the optimal scanning techniques for demonstrating uterine malignancy and discusses the role of imaging and the MRI appearances of uterine tumors.

Diffusion-weighted magnetic resonance imaging (DW-MRI) provides image contrast through measurement of the diffusion properties of water within tissues. Application of diffusion sensitising gradients to the MR pulse sequence allows water molecular displacement over distances of 1-20 microm to be recognised. Diffusion can be predominantly unidirectional (anisotropic) or not (isotropic). Combining images obtained with different amounts of diffusion weighting provides an apparent diffusion coefficient (ADC) map. In cancer imaging DW-MRI has been used to distinguish brain tumours from peritumoural oedema. It is also increasingly exploited to differentiate benign and malignant lesions in liver, breast and prostate where increased cellularity of malignant lesions restricts water motion in a reduced extracellular space. It is proving valuable in monitoring treatment where changes due to cell swelling and apoptosis are measurable as changes in ADC at an earlier stage than subsequent conventional radiological response indicators.

Background. Estimation of tumor volume by endovaginal magnetic resonance (MR) imaging is a better indicator of prognosis than FIGO stage in women with cervical cancer treated by standard modalities. However, the introduction of fertility conserving surgical techniques makes fresh demands upon imaging of these small tumors.Objective. To determine the sensitivity and specificity of endovaginal MRI in detecting small volume disease and assessing parametrial extension in uterine cervical cancer by comparing the findings with those at radical hysterectomy in order to establish its role in guiding the surgical decision-making process preoperatively.Methods. A retrospective study was performed in 119 patients who underwent endovaginal and external phased array MR imaging at 0.5 T or 1.5 T before radical hysterectomy. Tumor presence within the cervix and parametrial extension was noted on the endovaginal images. Histopathological findings were correlated with MR imaging results for all patients.Results. The sensitivity and specificity for detecting tumor by endovaginal MR imaging in the 119 patients were 96.9 and 59.0%, respectively. Thirty-six percent of tumors were < 1 cm(3) in volume. For these, sensitivity and specificity for tumor detection were 87% and 65% respectively. For evaluation of parametrial status, sensitivity was 80%, and specificity was 91.3%. A cut-off MRI tumor volume of 5.2 cm 3 predicted histologically confirmed lymph node metastases with a sensitivity of 78.6% and specificity of 72.5%.Conclusion. Endovaginal magnetic resonance imaging has high sensitivity in the preoperative staging of uterine cervical cancer even for tumors < 1 cm(3). It is an invaluable technique in planning fertility-conserving or radical surgical treatment of early stage cervical cancer. (c) 2005 Elsevier Inc. All rights reserved.

OBJECTIVE. We sought to describe MDCT and MRI features and tumor marker levels that differentiate borderline ovarian tumors from stage I ovarian tumors.CONCLUSION. Borderline ovarian tumors are complex masses with imaging features similar to stage I tumors. The thickness of septations and the size of solid components are significantly larger in stage I tumors, and these features may be helpful for predicting likelihood of invasive tumors. However, neither feature allows confident differentiation of borderline tumors from stage I disease.

The objective of this study is to assess tumour response to neoadjuvant chemotherapy prior to radical hysterectomy in cervical cancer using magnetic resonance (MR) to monitor tumour volume and changes in molecular profile and to compare the survival to that of a control group. Eligibility included Stage Ib-IIb previously untreated cervical tumours >10 cm(3). Neoadjuvant chemotherapy in 22 patients ( methotrexate 300 mg m(-2) (with folinic acid rescue), bleomycin 30 mg m(-2), cisplatin 60 mg m(-2)) was repeated twice weekly for three courses and followed by radical hysterectomy. Post-operative radiotherapy was given in 14 cases. A total of 23 patients treated either with radical surgery or chemoradiotherapy over the same time period comprised the nonrandomised control group. MR scans before and after neoadjuvant chemotherapy and in the control group documented tumour volume on imaging and metabolites on in vivo spectroscopy. Changes were compared using a paired t-test. Survival was calculated using the Kaplan-Meier method. There were no significant differences between the neoadjuvant chemotherapy and control groups in age ( mean, s.d. 43.3 +/- 10, 44.7 +/- 8.5 years, respectively, P = 0.63) or tumour volume (medians, quartiles 35.8, 17.8, 57.7 cm(3) vs 23.0, 15.0, 37.0 cm(3), respectively, P = 0.068). The reduction in tumour volume post-chemotherapy (median, quartiles 7.5, 3.0, 19.0 cm(3)) was significant ( P = 0.002). The reduction in - CH2 triglyceride approached significance ( P = 0.05), but other metabolites were unchanged. The 3-year survival in the chemotherapy group (49.1%) was not significantly different from the control group (46%, P = 0.94). There is a significant reduction in tumour volume and - CH2 triglyceride levels after neoadjuvant chemotherapy, but there is no survival advantage.