Visualizing the autonomic and somatic innervation of the female pelvis with 3D MR neurography: a feasibility study.

BACKGROUND: Treatment of female pelvic malignancies often causes pelvic nerve damage. Magnetic resonance (MR) neurography mapping the female pelvic innervation could aid in treatment planning. PURPOSE: To depict female autonomic and somatic pelvic innervation using a modified 3D NerveVIEW sequence. MATERIAL AND METHODS: Prospective study in 20 female volunteers (n = 6 normal, n = 14 cervical pathology) who underwent a modified 3D short TI inversion recovery (STIR) turbo spin-echo (TSE) scan with a motion-sensitive driven equilibrium (MSDE) preparation radiofrequency pulse and flow compensation. Modifications included offset independent trapezoid (OIT) pulses for inversion and MSDE refocusing. Maximum intensity projections (MIP) were evaluated by two observers (Observer 1, Observer 2); image quality was scored as 2 = high, 1 = medium, or 0 = low with the sciatic nerve serving as a reference. Conspicuity of autonomic superior (SHP) and bilateral inferior hypogastric plexuses (IHP), hypogastric nerves, and somatic pelvic nerves (sciatic, pudendal) was scored as 2 = well-defined, 1 = poorly defined, or 0 = not seen, and inter-observer agreement was determined. RESULTS: Images were of medium to high quality according to both observers agreeing in 15/20 (75%) of individuals. SHP and bilateral hypogastric nerves were seen in 30/60 (50%) of cases by both observers. Bilateral IHP was seen in 85% (34/40) by Observer 1 and in 75% (30/40) by Observer 2. Sciatic nerves were well identified in all cases, while pudendal nerves were seen bilaterally by Observer 1 in 65% (26/40) and by Observer 2 in 72.5% (29/40). Agreement between observers for scoring nerve conspicuity was in the range of 60%-100%. CONCLUSION: Modified 3D NerveVIEW renders high-quality images of the female autonomic and pudendal nerves.

Post-radiotherapy apparent diffusion coefficient (ADC) in children and young adults with high-grade gliomas and diffuse intrinsic pontine gliomas.

Objectives: Diffusion-weighted magnetic resonance imaging (DW-MRI) offers potential to monitor response and predict survival in high-grade gliomas (HGG) and diffuse intrinsic pontine gliomas (DIPG). We hypothesized that post-radiotherapy DW-MRI may provide prognostic imaging biomarkers in children and young adults with these tumors. Methods: Patients aged ≤21 years diagnosed between 2005 and 2012 were eligible. The tumor median apparent diffusion coefficient (ADC) and its 5th percentile (C5-ADC) were determined at the first post-radiotherapy scan and at the time of radiological progression. DW-MRI parameters were correlated with survival endpoints, temozolomide use and pseudoprogression, when it occurred. Results: Out of 40 patients (20 HGG, 20 DIPG), 23 had evaluable DW-MRI post-radiotherapy and 25 at radiological progression. There were 6 episodes of pseudoprogression. Hazard ratios (95%CI) for progression-free survival were 0.998 (0.993-1.003) for median ADC and 1.003 (0.996-1.010) for C5-ADC. Hazard ratios (95%CI) for overall survival were 1.0009 (0.996-1.006) for median ADC and 0.998 (0.992-1.004) for C5-ADC. Post-radiotherapy median and C5-ADC values were not significantly different between patients treated with radiotherapy alone versus radiotherapy/temozolomide. The median and C5-ADC values were not significantly different at the time of pseudoprogression compared to those at tumor progression. Conclusions: Post-radiotherapy median ADC and C5-ADC were not prognostic, nor able to differentiate radiosensitization with temozolomide or occurrence of pseudoprogression in this cohort of HGG and DIPG patients. Further exploration of alternative DW parameters, study timepoints or data modeling may contribute to the development of prognostic/predictive imaging biomarkers for children and young adults with HGG or DIPG.

Ultrasound Shear Wave Elastography of the Normal Prostate: Interobserver Reproducibility and Comparison with Functional Magnetic Resonance Tissue Characteristics.

The purpose of this study was to establish interobserver reproducibility of Young's modulus (YM) derived from ultrasound shear wave elastography (US-SWE) in the normal prostate and correlate it with multiparametric magnetic resonance imaging (mpMRI) tissue characteristics. Twenty men being screened for prostate cancer underwent same-day US-SWE (10 done by two blinded, newly-trained observers) and mpMRI followed by 12-core biopsy. Bland-Altman plots established limits of agreement for YM. Quantitative data from the peripheral zone (PZ) and the transitional zone (TZ) for YM, apparent diffusion coefficient (ADC, mm2/s from diffusion-weighted MRI), and Ktrans (volume transfer coefficient, min-1), Ve (extravascular-extracellular space, %), Kep (rate constant, /min), and initial area under the gadolinium concentration curve (IAUGC60, mmol/L/s) from dynamic contrast-enhanced MRI were obtained for slice-matched prostate sextants. Interobserver intraclass correlation coefficients were fair to good for individual regions (PZ = 0.57, TZ = 0.65) and for whole gland 0.67, (increasing to 0.81 when corrected for systematic observer bias). In the PZ, there were weak negative correlations between YM and ADC ( p = 0.008), and Ve ( p = 0.01) and a weak positive correlation with Kep ( p = 0.003). No significant intermodality correlations were seen in the TZ. Transrectal prostate US-SWE done without controlling manually applied probe pressure has fair/good interobserver reproducibility in inexperienced observers with potential to improve this to excellent by standardization of probe contact pressure. Within the PZ, increase in tissue stiffness is associated with reduced extracellular water (decreased ADC) and space (reduced Ve).

Diffusion-weighted Imaging as a Treatment Response Biomarker for Evaluating Bone Metastases in Prostate Cancer: A Pilot Study.

Purpose To determine the usefulness of whole-body diffusion-weighted imaging (DWI) to assess the response of bone metastases to treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and Methods A phase II prospective clinical trial of the poly-(adenosine diphosphate-ribose) polymerase inhibitor olaparib in mCRPC included a prospective magnetic resonance (MR) imaging substudy; the study was approved by the institutional research board, and written informed consent was obtained. Whole-body DWI was performed at baseline and after 12 weeks of olaparib administration by using 1.5-T MR imaging. Areas of abnormal signal intensity on DWI images in keeping with bone metastases were delineated to derive total diffusion volume (tDV); five target lesions were also evaluated. Associations of changes in volume of bone metastases and median apparent diffusion coefficient (ADC) with response to treatment were assessed by using the Mann-Whitney test and logistic regression; correlation with prostate-specific antigen level and circulating tumor cell count were assessed by using Spearman correlation (r). Results Twenty-one patients were included. All six responders to olaparib showed a decrease in tDV, while no decrease was observed in all nonresponders; this difference between responders and nonresponders was significant (P = .001). Increases in median ADC were associated with increased odds of response (odds ratio, 1.08; 95% confidence interval [CI]: 1.00, 1.15; P = .04). A positive association was detected between changes in tDV and best percentage change in prostate-specific antigen level and circulating tumor cell count (r = 0.63 [95% CI: 0.27, 0.83] and r = 0.77 [95% CI: 0.51, 0.90], respectively). When assessing five target lesions, decreases in volume were associated with response (odds ratio for volume increase, 0.89; 95% CI: 0.80, 0.99; P = .037). Conclusion This pilot study showed that decreases in volume and increases in median ADC of bone metastases assessed with whole-body DWI can potentially be used as indicators of response to olaparib in mCRPC. Online supplemental material is available for this article.

Separation of type and grade in cervical tumours using non-mono-exponential models of diffusion-weighted MRI.

OBJECTIVES: Assessment of empirical diffusion-weighted MRI (DW-MRI) models in cervical tumours to investigate whether fitted parameters distinguish between types and grades of tumours. METHODS: Forty-two patients (24 squamous cell carcinomas, 14 well/moderately differentiated, 10 poorly differentiated; 15 adenocarcinomas, 13 well/moderately differentiated, two poorly differentiated; three rare types) were imaged at 3 T using nine b-values (0 to 800 s mm-2). Mono-exponential, stretched exponential, kurtosis, statistical, and bi-exponential models were fitted. Model preference was assessed using Bayesian Information Criterion analysis. Differences in fitted parameters between tumour types/grades and correlation between fitted parameters were assessed using two-way analysis of variance and Pearson's linear correlation coefficient, respectively. RESULTS: Non-mono-exponential models were preferred by 83 % of tumours with bi-exponential and stretched exponential models preferred by the largest numbers of tumours. Apparent diffusion coefficient (ADC) and diffusion coefficients from non-mono-exponential models were significantly lower in poorly differentiated tumours than well/moderately differentiated tumours. α (stretched exponential), K (kurtosis), f and D* (bi-exponential) were significantly different between tumour types. Strong correlation was observed between ADC and diffusion coefficients from other models. CONCLUSIONS: Non-mono-exponential models were preferred to the mono-exponential model in DW-MRI data from cervical tumours. Parameters of non-mono-exponential models showed significant differences between types and grades of tumours. KEY POINTS: • Non-mono-exponential DW-MRI models are preferred in the majority of cervical tumours. • Poorly differentiated cervical tumours exhibit lower diffusion coefficients than well/moderately differentiated tumours. • Non-mono-exponential model parameters α, K, f, and D* differ between tumour types. • Micro-structural features are likely to affect parameters in non-mono-exponential models differently.

Diffusion-weighted (DW) MRI in lung cancers: ADC test-retest repeatability.

PURPOSE: To determine the test-retest repeatability of Apparent Diffusion Coefficient (ADC) measurements across institutions and MRI vendors, plus investigate the effect of post-processing methodology on measurement precision. METHODS: Thirty malignant lung lesions >2 cm in size (23 patients) were scanned on two occasions, using echo-planar-Diffusion-Weighted (DW)-MRI to derive whole-tumour ADC (b = 100, 500 and 800smm-2). Scanning was performed at 4 institutions (3 MRI vendors). Whole-tumour volumes-of-interest were copied from first visit onto second visit images and from one post-processing platform to an open-source platform, to assess ADC repeatability and cross-platform reproducibility. RESULTS: Whole-tumour ADC values ranged from 0.66-1.94x10-3mm2s-1 (mean = 1.14). Within-patient coefficient-of-variation (wCV) was 7.1% (95% CI 5.7-9.6%), limits-of-agreement (LoA) -18.0 to 21.9%. Lesions >3 cm had improved repeatability: wCV 3.9% (95% CI 2.9-5.9%); and LoA -10.2 to 11.4%. Variability for lesions <3 cm was 2.46 times higher. ADC reproducibility across different post-processing platforms was excellent: Pearson's R2 = 0.99; CoV 2.8% (95% CI 2.3-3.4%); and LoA -7.4 to 8.0%. CONCLUSION: A free-breathing DW-MRI protocol for imaging malignant lung tumours achieved satisfactory within-patient repeatability and was robust to changes in post-processing software, justifying its use in multi-centre trials. For response evaluation in individual patients, a change in ADC >21.9% will reflect treatment-related change. KEY POINTS: • In lung cancer, free-breathing DWI-MRI produces acceptable images with evaluable ADC measurement. • ADC repeatability coefficient-of-variation is 7.1% for lung tumours >2 cm. • ADC repeatability coefficient-of-variation is 3.9% for lung tumours >3 cm. • ADC measurement precision is unaffected by the post-processing software used. • In multicentre trials, 22% increase in ADC indicates positive treatment response.

Monitoring Tumor Volume in Patients With Prostate Cancer Undergoing Active Surveillance: Is MRI Apparent Diffusion Coefficient Indicative of Tumor Growth?

OBJECTIVE: The purpose of this study was to measure longitudinal change in tumor volume of the dominant intraprostatic lesion and determine whether baseline apparent diffusion coefficient (ADC) and change in ADC are indicative of tumor growth in patients with prostate cancer undergoing active surveillance. SUBJECTS AND METHODS: The study group included 151 men (mean age, 68.1 ± 7.4 [SD] years; range, 50-83 years) undergoing active surveillance with 3D whole prostate, zonal, and tumor volumetric findings documented at endorectal MRI examinations performed at two time points (median interval, 1.9 years). Tumor (location confirmed at transrectal ultrasound or template biopsy) ADC was measured on the slice with the largest lesion. Twenty randomly selected patients had the measurements repeated by the same observer after a greater than 4-month interval, and the limits of agreement of measurements were calculated. Tumor volume increases greater than the upper limit of agreement were designated measurable growth, and their baseline ADCs and change in ADC were compared with those of tumors without measurable growth (independent-samples t test). RESULTS: Fifty-two (34.4%) tumors increased measurably in volume. Baseline ADC and tumor volume were negatively correlated (r = -0.42, p = 0.001). Baseline ADC values did not differ between those with and those without measurable growth (p = 0.06), but change in ADC was significantly different (-6.8% ± 12.3% for those with measurable growth vs 0.23% ± 10.1% for those without, p = 0.0005). Percentage change in tumor volume and percentage change in ADC were negatively correlated (r = -0.31, p = 0.0001). A 5.8% reduction in ADC indicated a measurable increase in tumor volume with 54.9% sensitivity and 77.0% specificity (AUC, 0.67). CONCLUSION: Tumor volume increased measurably in 34.4% of men after 2 years of active surveillance. Change in ADC may be used to identify tumors with measurable growth.

Distortion correction of echo-planar diffusion-weighted images of uterine cervix.

PURPOSE: To investigate the clinical utility of the reverse gradient algorithm in correcting distortions in diffusion-weighted images of the cervix and for increasing diagnostic performance. MATERIALS AND METHODS: Forty-one patients ages 25-72 years (mean 40 ± 11 years) with suspected or early stage cervical cancer were imaged at 3T using an endovaginal coil. T2 -weighted (W) and diffusion-weighted images with right and left phase-encode gradient directions were obtained coronal to the cervix (b = 0, 100, 300, 500, 800 s mm(-2) ). Differences in angle of the endocervical canal to the x-axis between T2 W and right-gradient, left-gradient, and corrected images were measured. Uncorrected and corrected images were assessed for diagnostic performance when viewed together with T2 W images by two independent observers against subsequent histology. RESULTS: The angles of the endocervical canal relative to the x-axis were significantly different between the T2 W images and the right-gradient images (P = 0.007), approached significance for left-gradient images (P = 0.055), and were not significantly different after correction (P = 0.95). Corrected images enabled a definitive diagnosis in 34% (n = 14) of patients classified as equivocal on uncorrected images. Tumor volume in this subset was 0.18 ± 0.44 cm(3) (mean ± SD; sensitivity of detection 100% [8/8], specificity 50% [3/6] for an experienced observer). Correction did not improve diagnostic performance for the less-experienced observer. CONCLUSION: Distortion-corrected diffusion-weighted images improved correspondence with T2 W images and diagnostic performance in a third of cases.

Diffusion-weighted MR imaging of metastatic abdominal and pelvic tumours is sensitive to early changes induced by a VEGF inhibitor using alternative diffusion attenuation models.

OBJECTIVES: To assess the utility of diffusion weighted imaging for monitoring early treatment effects associated with a VEGF inhibitor. MATERIALS AND METHODS: Twenty-nine patients with metastatic abdominal and pelvic tumours were recruited and imaged with DW-MRI: twice at baseline, and after 7 and 28 days of treatment with cediranib. Tumour measures were derived using mono-exponential, bi-exponential and stretched-exponential models, and parameter repeatability and treatment effects seen after 7 and 28 days were assessed. Correlations with volume changes and DCE-MRI metrics were also assessed. RESULTS: Diffusion coefficient repeatabilities from all models were < 6%; f and D* (bi-exponential) were 22% and 44%; α (stretched-exponential) was 4.2%. Significant increases in the diffusion coefficients from all models were observed at day 28 but not day 7. Significant decreases in D* and f.D* were observed at day 7 and in f at day 28; significant increases in α were observed at both time-points. Weak correlations between DW-MRI changes and volume changes and DCE-MRI changes were observed. CONCLUSION: DW-MRI is sensitive to early and late treatment changes caused by a VEGF inhibitor using non-mono-exponential models. Evidence of over-fitting using the bi-exponential model suggests that the stretched-exponential model is best suited to monitor such changes. KEY POINTS: • Non-mono-exponential diffusion models widen sensitivity to a broader class of tissue properties. • A stretched-exponential model robustly detects changes after 7 days of VEGF-inhibitor treatment. • There are very weak correlations between DWI-IVIM perfusion and similar DCE-MRI measures. • Diffusion-weighted MRI is a highly informative technique for assessing novel tumour therapies.

Comparison of optimised endovaginal vs external array coil T2-weighted and diffusion-weighted imaging techniques for detecting suspected early stage (IA/IB1) uterine cervical cancer.

OBJECTIVE: To compare sensitivity and specificity of endovaginal versus external-array coil T2-W and T2-W + DWI for detecting and staging small cervical tumours. METHODS: Optimised endovaginal and external array coil MRI at 3.0-T was done prospectively in 48 consecutive patients with stage Ia/Ib1 cervical cancer. Sensitivity/specificity for detecting tumour and parametrial extension against histopathology for a reading radiologist were determined on coronal T2-W and T2W + DW images. An independent radiologist also scored T2-W images without and with addition of DWI for the external-array and endovaginal coils on separate occasions >2 weeks apart. Cohen's kappa assessed inter- and intra-observer agreement. RESULTS: Median tumour volume in 19/38 cases positive on subsequent histology was 1.75 cm(3). Sensitivity, specificity, PPV, NPV were: reading radiologist 91.3 %, 89.5 %, 91.3 %, 89.5 %, respectively; independent radiologist T2-W 82.6 %, 73.7 %, 79.1 %, 77.8 % for endovaginal, 73.9 %, 89.5 %, 89.5 %, 73.9 % for external-array coil. Adding DWI improved sensitivity and specificity of endovaginal imaging (78.2 %, 89.5 %); adding DWI to external-array imaging improved specificity (94.7 %) but reduced sensitivity (66.7 %). Inter- and intra-observer agreement on T2-W + DWI was good (kappa = 0.67 and 0.62, respectively). CONCLUSION: Endovaginal coil T2-W MRI is more sensitive than external-array coil for detecting tumours <2 cm(3); adding DWI improves specificity of endovaginal imaging but reduces sensitivity of external-array imaging. KEY POINTS: • Endovaginal more accurate than external-array T2-W MRI for detecting small cervical cancers. • Addition of DWI improves sensitivity and specificity of endovaginal T2-W imaging. • Addition of DWI substantially reduces sensitivity of external-array T2-W imaging.

TE = 32 ms vs TE = 100 ms echo-time (1)H-magnetic resonance spectroscopy in prostate cancer: Tumor metabolite depiction and absolute concentrations in tumors and adjacent tissues.

PURPOSE: To compare the depiction of metabolite signals in short and long echo time (TE) prostate cancer spectra at 3T, and to quantify their concentrations in tumors of different stage and grade, and tissues adjacent to tumor. MATERIALS AND METHODS: First, single-voxel magnetic resonance imaging (MRI) spectra were acquired from voxels consisting entirely of tumor, as defined on T2-weighted and diffusion-weighted (DW)-MRI and from a biopsy-positive octant, at TEs of 32 msec and 100 msec in 26 prostate cancer patients. Then, in a separate cohort of 26 patients, single-voxel TE = 32 msec MR spectroscopy (MRS) was performed over a partial-tumor region and a matching, contralateral normal-appearing region, defined similarly. Metabolite depiction was compared between TEs using Cramér-Rao lower bounds (CRLB), and absolute metabolite concentrations were calculated from TE = 32 msec spectra referenced to unsuppressed water spectra. RESULTS: Citrate and spermine resonances in tumor were better depicted (had significantly lower CRLB) at TE = 32 msec, while the choline resonance was better depicted at TE = 100 msec. Citrate and spermine concentrations were significantly lower in patients of more advanced stage, significantly lower in Gleason grade 3+4 than 3+3 tumors, and significantly lower than expected from the tumor fraction in partial-tumor voxels (by 14 mM and 4 mM, respectively, P < 0.05). CONCLUSION: Citrate and spermine resonances are better depicted at short TE than long TE in tumors. Reduction in these concentrations is related to increasing tumor stage and grade in vivo, while reductions in the normal-appearing tissues immediately adjacent to tumor likely reflect tumor field effects.

Whole-body diffusion-weighted MR imaging for assessment of treatment response in myeloma.

PURPOSE: To determine the feasibility of whole-body diffusion-weighted (DW) magnetic resonance (MR) imaging for assessment of treatment response in myeloma. MATERIALS AND METHODS: This prospective single-institution study was HIPAA-compliant with local research ethics committee approval. Written informed consent was obtained from each subject. Eight healthy volunteers (cohort 1a) and seven myeloma patients (cohort 1b) were imaged twice to assess repeatability of quantitative apparent diffusion coefficient (ADC) estimates. Thirty-four additional myeloma patients (cohort 2) underwent whole-body DW imaging before treatment; 26 completed a posttreatment imaging. Whole-body DW data were compared before and after treatment by using qualitative (ie, observer scores) and quantitative (ie, whole-body segmentation of marrow ADC) methods. Serum paraproteins and/or light chains or bone marrow biopsy defined response. RESULTS: Whole-body DW imaging scores were significantly different between observers (P < .001), but change in scores between observers after treatment was not (P = .49). Sensitivity and specificity for detecting response according to observer scores were 86% (18 of 21 patients) and 80% (4 of 5 patients) for both observers. ADC measurement was repeatable: mean coefficient of variation was 3.8% in healthy volunteers and 2.8% in myeloma patients. Pretreatment ADC in cohort 2 was significantly different from that in cohort 1a (P = .03), but not from that in cohort 1b (P = .2). Mean ADC increased in 95% (19 of 20) of responding patients and decreased in all (five of five) nonresponders (P = .002). A 3.3% increase in ADC helped identify response with 90% sensitivity and 100% specificity; an 8% increase (greater than repeatability of cohort 1b) resulted in 70% sensitivity and 100% specificity. There was a significant negative correlation between change in ADC and change in laboratory markers of response (r = -0.614; P = .001). CONCLUSION: Preliminary work demonstrates whole-body DW imaging is a repeatable, quantifiable technique for assessment of treatment response in myeloma.

Preoperative imaging in patients undergoing trachelectomy for cervical cancer: validation of a combined T2- and diffusion-weighted endovaginal MRI technique at 3.0 T.

AIM: The aim of this study is to validate high-resolution endovaginal T2- and diffusion-weighted MRI measurements (tumour size, volume and length of uninvolved cervical canal) against histology in patients undergoing trachelectomy. PATIENTS/INTERVENTIONS: 55 consecutive patients 25-44 years with cervical cancer being considered for trachelectomy were prospectively assessed with endovaginal T2-W and diffusion-weighted MRI. Two independent observers blinded to histology recorded maximum tumour dimension, volume and distance from the superior aspect of the tumour to the internal os. Following trachelectomy, pathologist-outlined tumour sections were photographed with a set scale and similar measurements were recorded. RESULTS: Fifteen of 45 patients subsequently treated with fertility-sparing surgery had residual tumour (median histological volume: 0.28 cm(3), IQR=0.14-1.06 cm(3)). Sensitivity, specificity, positive and negative predictive values for detecting tumour: Observer 1: 86.7%, 80.0%, 68.4%, and 92.3%, respectively; Observer 2: 86.7%, 90.0%, 81.0%, and 93.1%, respectively. Size and volume correlated between observers (r=0.96, 0.84, respectively, p<0.0001). Size correlated between each observer and histology (observer 1 r=0.91, p<0.0001; observer 2 r=0.93, p<0.0001), volume did not (observer 1: r=0.08, p=0.6; observer 2: r=0.21, p=0.16); however, differences between observer measurements and histology were not significant (size p=0.09, volume p=0.15). Differences between MRI and histology estimates of endocervical canal length were not significant (p=0.1 both observers). CONCLUSION: In subcentimetre cervical cancers, endovaginal MRI correlates with pathology and is invaluable in assessing patients for fertility-sparing surgery.

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.

Advanced solid tumors treated with cediranib: comparison of dynamic contrast-enhanced MR imaging and CT as markers of vascular activity.

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.

Diffusion weighted imaging of the normal breast: reproducibility of apparent diffusion coefficient measurements and variation with menstrual cycle and menopausal status.

OBJECTIVES: To establish the reproducibility of apparent diffusion coefficient (ADC) measurements in normal fibroglandular breast tissue and to assess variation in ADC values with phase of the menstrual cycle and menopausal status. METHODS: Thirty-one volunteers (13 premenopausal, 18 postmenopausal) underwent magnetic resonance twice (interval 11-22 days) using diffusion-weighted MRI. ADC(total) and a perfusion-insensitive ADC(high) (omitting b = 0) were calculated. Reproducibility and inter-observer variability of mean ADC values were assessed. The difference in mean ADC values between the two phases of the menstrual cycle and the postmenopausal breast were evaluated. RESULTS: ADC(total) and ADC(high) showed good reproducibility (r% = 17.6, 22.4). ADC(high) showed very good inter-observer agreement (kappa = 0.83). The intraclass correlation coefficients (ICC) were 0.93 and 0.91. Mean ADC values were significantly lower in the postmenopausal breast (ADC(total) 1.46 ± 0.3 × 10(-3) mm(2)/s, ADC(high) 1.33 ± 0.3 × 10(-3) mm(2)/s) compared with the premenopausal breast (ADC(total) 1.84 ± 0.26 × 10(-3) mm(2)/s, ADC(high) 1.77 ± 0.26 × 10(-3) mm(2)/s; both P < 0.001). No significant difference was seen in ADC values in relation to menstrual cycle (ADC(total) P = 0.2, ADC(high) P = 0.24) or between postmenopausal women taking or not taking oestrogen supplements (ADC(total) P = 0.6, ADC(high) P = 0.46). CONCLUSIONS: ADC values in fibroglandular breast tissue are reproducible. Lower ADC values within the postmenopausal breast may reduce diffusion-weighted contrast and have implications for accurately detecting tumours. KEY POINTS: • ADC values from fibroglandular breast tissue are measured reproducibly by multiple observers. • Mean ADC values were significantly lower in postmenopausal than premenopausal breast tissue. • Mean ADC values did not vary significantly with menstrual cycle. • Low postmenopausal ADC values may hinder tumour detection on DW-MRI.

Diffusion-weighted MRI for locally recurrent prostate cancer after external beam radiotherapy.

OBJECTIVE: 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. MATERIALS AND METHODS: Twenty-four patients with rising prostate-specific antigen levels after having completed radiation therapy 30-130 months earlier (median, 62 months) underwent endorectal T2-weighted imaging and DWI (b = 0, 100, 300, 500, and 800 s/mm(2)) followed by transrectal ultrasound (TRUS)-guided biopsy. Images were scored prospectively as positive for tumor if a region of low signal intensity on T2-weighted imaging within the prostate corresponded with a focally restricted area on the ADC map. A region of interest (ROI) was drawn around the suspicious lesion on a single slice of the ADC map and a corresponding ROI was drawn around presumed nontumor irradiated peripheral zone and central gland tissues on the opposite side of the prostate. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined against TRUS-guided biopsy reference standard (octant, n = 17; sextant, n = 5; two samples, n = 1; 12 samples, n = 1). RESULTS: Sixteen of 24 patients (66.7%) had positive histology findings. The median tumor ROI area was 0.37 cm(2) (quartiles, 0.30 and 0.82 cm(2)). The sensitivity, specificity, PPV, and NPV for detecting tumor were 93.8%, 75%, 88.2%, and 85.7%, respectively. A cutoff ADC of 1216 × 10(-6) mm(2)/s could predict tumor with 100% sensitivity and 96% specificity (area under the receiver operating characteristic curve = 0.992). CONCLUSION: An ADC derived from DWI is a useful adjunct to T2-weighted MRI for detecting local tumor recurrence larger than 0.4 cm(2) within the prostate.

Endovaginal magnetic resonance imaging of stage 1A/1B cervical cancer with A T2- and diffusion-weighted magnetic resonance technique: effect of lesion size and previous cone biopsy on tumor detectability.

OBJECTIVE: 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. METHODS: One hundred and thirteen patients with cervical tumor were imaged using an endovaginal coil with T2-weighted (T2-W) and diffusion-weighted single-shot echo-planar sequences; 85 managed surgically (58 with prior cone biopsy/LLETZ) were evaluated. T2-W images and ADC maps viewed simultaneously were scored positive or negative for tumor and compared with histology at surgery. MRI tumor volumes, maximum radiological and histological dimensions were recorded. ROC analysis determined the MRI volume with optimal sensitivity/specificity for identifying tumor in those without and with prior cone biopsy/LLETZ and the maximum histological dimension for correctly identifying tumor with MRI. Mean apparent diffusion coefficients (ADCs) from tumor and adjacent normal epithelium were compared. RESULTS: Sensitivity and specificity for detecting tumor in those without (100%; 100% respectively) and with (80%; 78.9% respectively) prior cone biopsy/LLETZ were significantly different (p<0.001). Following cone biopsy/LLETZ, MRI tumor volume of 83 mm3 detected tumor with 80% sensitivity, 94.7% specificity; a 5.3mm maximal histological dimension was detected on MRI with 100% sensitivity, 100% specificity. Tumor ADCs were significantly lower (p<0.001) than paired normal epithelial tissue (median, 988×10(-6) mm2/s vs. 1564×10(-6) mm2/s) but neither tumor nor epithelial ADCs differed significantly between patients with or without prior cone biopsy/LLETZ (p=0.48 and 0.15, respectively). CONCLUSIONS: Endovaginal MRI with T2- and diffusion-weighted sequences has significantly lower sensitivity and specificity for tumor detection following cone biopsy/LLETZ.

Apparent diffusion coefficient as a predictive biomarker of prostate cancer progression: value of fast and slow diffusion components.

OBJECTIVE: 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. SUBJECTS AND METHODS: Eighty-one patients managed by active surveillance underwent diffusion-weighted MRI in addition to T2-weighted MRI using an endorectal technique. ADCs from tumor regions of interest were calculated using all b values (ADC(all)), b = 0-300 s/mm(2) (ADC(fast)), and b = 300-800 s/mm(2) (ADC(slow)). These parameters and tumor volumes were compared in those upgraded at subsequent biopsy (n = 14) versus those histologically stable (n = 41) and in evaluable patients who progressed to radical treatment (n = 16) versus those who did not (n = 64). Cox's regression was used to analyze the effect of parameter mean on time to treatment. RESULTS: ADC(all), ADC(fast), and ADC(slow) in patients upgraded on repeat biopsy were significantly lower than those who were stable (1,070 ± 110 vs 1,356 ± 357 × 10(-6)mm(2)/s, p < 0.001; 1,283 ± 188 vs 1,526 ± 397 × 10(-6)mm(2)/s, p = 0.004; 843 ± 74 vs 1,105 ± 285 × 10(-6) mm(2)/s, p < 0.001, respectively). Tumor volume was significantly higher in the upgraded group (0.86 ± 0.9 vs 0.26 ± 0.25 cm(3), p = 0.02). The lower ADC(slow) in patients who subsequently progressed to radical treatment approached significance (922 ± 256 vs 1,054 ± 235 × 10(-6) mm(2)/s, p = 0.053; hazard ratio, 0.991 for time to treatment). Tumor volume was significantly higher in the treated group (0.86 ± 0.85 cm(3) vs 0.32 ± 0.33 cm(3), p = 0.02). ADC(slow) and tumor volume were significant but independent predictors of upgrade on biopsy (p = 0.01 and 0.002, respectively). CONCLUSION: Both fast and slow diffusion components were significantly lower in tumors that were subsequently upgraded on histology. Both tumor volume and the true diffusion ADC(slow) were significant but independent predictors of histologic progression.

Prospective Evaluation of Whole-Body MRI versus FDG PET/CT for Lesion Detection in Participants with Myeloma.

Purpose To compare disease detection of myeloma using contemporary whole-body (WB) MRI and fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT protocols and to correlate imaging with laboratory estimates of disease burden, including molecular characteristics. Materials and Methods In this observational, prospective study, participants were recruited from November 2015 to March 2018 who had a diagnosis of myeloma, who were planned to undergo chemotherapy and autologous stem cell transplantation, and who underwent baseline WB-MRI and FDG PET/CT (ClinicalTrials.gov identifier NCT02403102). Baseline clinical data, including genetics, were collected. Paired methods were used to compare burden and patterns of disease. Results Sixty participants (mean age, 60 years ± 9 [standard deviation]; 35 men) underwent baseline WB-MRI and FDG PET/CT. WB-MRI showed significantly higher detection for focal lesions at all anatomic sites (except ribs, scapulae, and clavicles) and for diffuse disease at all sites. Two participants presented with two or more focal lesions smaller than 5 mm only at WB-MRI but not FDG PET/CT. Participants with diffuse disease at MRI had higher plasma cell infiltration (percentage of nucleated cells: median, 60% [interquartile range {IQR}, 50%-61%] vs 15% [IQR, 4%-50%]; P = .03) and paraprotein levels (median, 32.0 g/L [IQR, 24.0-48.0 g/L] vs 20.0 g/L [IQR, 12.0-22.6 g/L]; P = .02) compared with those without diffuse disease. All genetically high-risk tumors showed diffuse infiltration at WB-MRI. Conclusion WB-MRI helped detect a higher number of myeloma lesions than FDG PET/CT, and diffuse disease detected at WB-MRI correlated with laboratory measures of disease burden and molecular markers of risk. Keywords: MR-Imaging, Skeletal-Appendicular, Skeletal-Axial, Bone Marrow, Hematologic Diseases, Oncology Clinical trial registration no. NCT02403102. Supplemental material is available for this article. © RSNA, 2021.