Diffusion‐weighted imaging features of breast tumours and the surrounding stroma reflect intrinsic heterogeneous characteristics of molecular subtypes in breast cancer

Breast cancer heterogeneity is the main obstacle preventing the identification of patients with breast cancer with poor prognoses and treatment responses; however, such heterogeneity has not been well characterized. The purpose of this retrospective study was to reveal heterogeneous patterns in the apparent diffusion coefficient (ADC) signals in tumours and the surrounding stroma to predict molecular subtypes of breast cancer. A dataset of 126 patients with breast cancer, who underwent preoperative diffusion‐weighted imaging (DWI) on a 3.0‐T image system, was collected. Breast images were segmented into regions comprising the tumour and surrounding stromal shells in which features that reflect heterogeneous ADC signal distribution were extracted. For each region, imaging features were computed, including the mean, minimum, variance, interquartile range (IQR), range, skewness, kurtosis and entropy of ADC values. Univariate and stepwise multivariate logistic regression modelling was performed to identify the magnetic resonance imaging features that optimally discriminate luminal A, luminal B, human epidermal growth factor 2 (HER2)‐enriched and basal‐like molecular subtypes. The performance of the predictive models was evaluated using the area under the receiver operating characteristic curve (AUC). Univariate logistic regression analysis showed that the skewness in the tumour boundary achieved an AUC of 0.718 for discrimination between luminal A and non‐luminal A tumours, whereas the IQR of the ADC value in the tumour boundary had an AUC of 0.703 for classification of the HER2‐enriched subtype. Imaging features in the tumour boundary and the proximal peritumoral stroma corresponded to a higher overall prediction performance than those in other regions. A multivariate logistic regression model combining features in all the regions achieved an overall AUC of 0.800 for the classification of the four tumour subtypes. These findings suggest that features in the tumour boundary and stroma around the tumour may be further assessed as potential predictors of molecular subtypes of breast cancer.     

Comparing diagnostic accuracy of luminal water imaging with diffusion‐weighted and dynamic contrast‐enhanced MRI in prostate cancer: A quantitative MRI study

Luminal water imaging (LWI) is a new MRI T₂ mapping technique that has been developed with the aim of diagnosis of prostate carcinoma (PCa). This technique measures the fractional amount of luminal water in prostate tissue, and has shown promising preliminary results in detection of PCa. To include LWI in clinical settings, further investigation on the accuracy of this technique is required. In this study, we compare the diagnostic accuracy of LWI with those of diffusion‐weighted imaging (DWI) and dynamic contrast‐enhanced (DCE) MRI in detection and grading of PCa. Fifteen patients with biopsy‐proven PCa consented to participate in this ethics‐board‐approved prospective study. Patients were examined with LWI, DWI, and DCE sequences at 3 T prior to radical prostatectomy. Maps of MRI parameters were generated and registered to whole‐mount histology. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic accuracy of individual and combined MR parameters. Correlation with Gleason score (GS) was evaluated using Spearman's rank correlation test. The results show that area under the ROC curve (AUC) obtained from LWI was equal to or higher than the AUC obtained from DWI, DCE, or their combination, in peripheral zone (0.98 versus 0.90, 0.89, and 0.91 respectively), transition zone (0.99 versus 0.98, n/a, and 0.98), and the entire prostate (0.85 versus 0.81, 0.75, and 0.84). The strongest correlation with GS was achieved from LWI (ρ = ?0.81 ± 0.09, P < 0.001). Results of this pilot study show that LWI performs equally well as, or better than, DWI and DCE in detection of PCa. LWI provides significantly higher correlation with GS than DWI and DCE. This technique can potentially be included in clinical MRI protocols to improve characterization of tumors. However, considering the small size of the patient population in this study, a further study with a larger cohort of patients and broader range of GS is required to confirm the findings and draw a firm conclusion on the applicability of LWI in clinical settings.     

Diffusion‐weighted MRI measurements on stroke patients reveal water‐exchange mechanisms in sub‐acute ischaemic lesions

The aim of this study was to investigate the diffusion time dependence of signal‐versus‐b curves obtained from diffusion‐weighted magnetic resonance imaging (DW‐MRI) of sub‐acute ischaemic lesions in stroke patients. In this case series study, 16 patients with sub‐acute ischaemic stroke were examined with DW‐MRI using two different diffusion times (60 and 260 ms). Nine of these patients showed sufficiently large lesions without artefacts to merit further analysis. The signal‐versus‐b curves from the lesions were plotted and analysed using a two‐compartment model including compartmental exchange. To validate the model and to aid the interpretation of the estimated model parameters, Monte Carlo simulations were performed. In eight cases, the plotted signal‐versus‐b curves, obtained from the lesions, showed a signal–curve split‐up when data for the two diffusion times were compared, revealing effects of compartmental water exchange. For one of the patients, parametric maps were generated based on the extracted model parameters. These novel observations suggest that water exchange between different water pools is measurable and thus potentially useful for clinical assessment. The information can improve the understanding of the relationship between the DW‐MRI signal intensity and the microstructural properties of the lesions. Copyright © 2009 John Wiley & Sons, Ltd.     

Diffusion‐weighted imaging of the abdomen: Impact of b‐values on texture analysis features

The purpose of this work was to systematically assess the impact of the b‐value on texture analysis in MR diffusion‐weighted imaging (DWI) of the abdomen. In eight healthy male volunteers, echo‐planar DWI sequences at 16 b‐values ranging between 0 and 1000 s/mm² were acquired at 3 T. Three different apparent diffusion coefficient (ADC) maps were computed (0, 750/100, 390, 750 s/mm²/all b‐values). Texture analysis of rectangular regions of interest in the liver, kidney, spleen, pancreas, paraspinal muscle and subcutaneous fat was performed on DW images and the ADC maps, applying 19 features computed from the histogram, grey‐level co‐occurrence matrix (GLCM) and grey‐level run‐length matrix (GLRLM). Correlations between b‐values and texture features were tested with a linear and an exponential model; the best fit was determined by the smallest sum of squared residuals. Differences between the ADC maps were assessed with an analysis of variance. A Bonferroni‐corrected p‐value less than 0.008 (=0.05/6) was considered statistically significant. Most GLCM and GLRLM‐derived texture features (12–18 per organ) showed significant correlations with the b‐value. Four texture features correlated significantly with changing b‐values in all organs (p < 0.008). Correlation coefficients varied between 0.7 and 1.0. The best fit varied across different structures, with fat exhibiting mostly exponential (17 features), muscle mostly linear (12 features) and the parenchymatous organs mixed feature alterations. Two GLCM features showed significant variability in the different ADC maps. Several texture features vary systematically in healthy tissues at different b‐values, which needs to be taken into account if DWI data with different b‐values are analyzed. Histogram and GLRLM‐derived texture features are stable on ADC maps computed from different b‐values.     

Sequence design and evaluation of the reproducibility of water‐selective diffusion‐weighted imaging of the breast at 3 T

Diffusion measurements derived from breast MRI can be adversely affected by unwanted signals from abundant fatty tissues if they are not suppressed adequately. To minimize this undesired contribution, we designed and optimized a water‐selective diffusion‐weighted imaging (DWI) sequence, which relies on spectrally selective excitation on the water resonance, obviating the need for fat suppression. As this method is more complex than standard DWI methods, we also report a test–retest study to evaluate its reproducibility. In this study, a spectrally selective Gaussian pulse on water resonance was combined with a pair of slice‐selective adiabatic refocusing pulses for water‐only DWI. Field map‐based shimming and manual determination of the center frequency were used for water selection. The selectivity of the excitation pulse was optimized by a spectrally selective spectroscopy sequence based on the same principles. A test–retest study of 10 volunteers in two separate visits was used to evaluate its reproducibility. Our results from all subjects showed high‐quality diffusion‐weighted images of the breast without fat contamination. Mean apparent diffusion coefficients for b = 0, 600 s/mm² and b = 50, 600 s/mm² all showed good reproducibility, as 95% confidence intervals of the apparent diffusion coefficients were 4 × 10^–5 mm²/s and 5 × 10^–5 mm²/s and repeatability values were 1.09 × 10^–4 and 1.31 × 10^–4, respectively. In conclusion, water‐selective DWI is a feasible alternative to standard methods of DWI based on fat suppression. The added complexity of the method does not compromise the reproducibility of diffusion measurements in the breast. Copyright © 2014 John Wiley & Sons, Ltd.     

Tractography of the optic radiation: a repeatability and reproducibility study

Our main objective was to evaluate the repeatability and reproducibility of optic radiation (OR) reconstruction from diffusion MRI (dMRI) data. 14 adults were scanned twice with the same 60‐direction dMRI sequence. Peaks in the diffusion profile were estimated with the single tensor (ST), Q‐ball (QSH) and persistent angular structure (PAS) methods. Segmentation of the OR was performed by two experimenters with probabilistic tractography based on a manually drawn region‐of‐interest (ROI) protocol typically employed for OR segmentation, with both standard and extended sets of ROIs. The repeatability and reproducibility were assessed by calculating the intra‐class correlation coefficient (ICC) of intra‐ and inter‐rater experiments, respectively. ICCs were calculated for commonly used dMRI metrics (FA, MD, AD, RD) and anatomical dimensions of the optic radiation (distance from Meyer's loop to the temporal pole, ML‐TP), as well as the Dice similarity coefficient (DSC) between the raters’ OR segmentation. Bland–Altman plots were also calculated to investigate bias and variability in the reproducibility measurements. The OR was successfully reconstructed in all subjects by both raters. The ICC was found to be in the good to excellent range for both repeatability and reproducibility of the dMRI metrics, DSC and ML‐TP distance. The Bland–Altman plots did not show any apparent systematic bias for any quantities. Overall, higher ICC values were found for the multi‐fiber methods, QSH and PAS, and for the standard set of ROIs. Considering the good to excellent repeatability and reproducibility of all the quantities investigated, these findings support the use of multi‐fiber OR reconstruction with a limited number of manually drawn ROIs in clinical applications utilizing either OR microstructure characterization or OR dimensions, as is the case in neurosurgical planning for temporal lobectomy. Copyright © 2015 John Wiley & Sons, Ltd.     

Diffusion‐weighted MRI monitoring of pancreatic cancer response to radiofrequency heat‐enhanced intratumor chemotherapy

The aim of this study was to evaluate the feasibility of using diffusion‐weighted MRI to monitor the early response of pancreatic cancers to radiofrequency heat (RFH)‐enhanced chemotherapy. Human pancreatic carcinoma cells (PANC‐1) in different groups and 24 mice with pancreatic cancer xenografts in four groups were treated with phosphate‐buffered saline (PBS) as a control, RFH at 42 °C, gemcitabine and gemcitabine plus RFH at 42 °C. One day before and 1, 7 and 14 days after treatment, diffusion‐weighted MRI and T₂‐weighted imaging were applied to monitor the apparent diffusion coefficients (ADCs) of tumors and tumor growth. MRI findings were correlated with the results of tumor apoptosis analysis. In the in vitro experiments, the quantitative viability assay showed lower relative cell viabilities for treatment with gemcitabine plus RFH at 42 °C relative to treatment with RFH only and gemcitabine only (37 ± 5% versus 65 ± 4% and 58 ± 8%, respectively, p < 0.05). In the in vivo experiments, the combination therapy resulted in smaller relative tumor volumes than RFH only and chemotherapy only (0.82 ± 0.17 versus 2.23 ± 0.90 and 1.64 ± 0.44, respectively, p = 0.003). In vivo, 14‐T MRI demonstrated a remarkable decrease in ADCs at day 1 and increased ADCs at days 7 and 14 in the combination therapy group. The apoptosis index in the combination therapy group was significantly higher than those in the chemotherapy‐only, RFH‐only and PBS treatment groups (37 ± 6% versus 20 ± 5%, 8 ± 2% and 3 ± 1%, respectively, p < 0.05). This study confirms that it is feasible to use MRI to monitor RFH‐enhanced chemotherapy in pancreatic cancers, which may present new options for the efficient treatment of pancreatic malignancies using MRI/RFH‐integrated local chemotherapy. Copyright © 2013 John Wiley & Sons, Ltd.     

Multi‐center evaluation of stability and reproducibility of quantitative MRI measures in healthy calf muscles

The purpose of this study was to evaluate temporal stability, multi‐center reproducibility and the influence of covariates on a multimodal MR protocol for quantitative muscle imaging and to facilitate its use as a standardized protocol for evaluation of pathology in skeletal muscle. Quantitative T2, quantitative diffusion and four‐point Dixon acquisitions of the calf muscles of both legs were repeated within one hour. Sixty‐five healthy volunteers (31 females) were included in one of eight 3‐T MR systems. Five traveling subjects were examined in six MR scanners. Average values over all slices of water‐T2 relaxation time, proton density fat fraction (PDFF) and diffusion metrics were determined for seven muscles. Temporal stability was tested with repeated measured ANOVA and two‐way random intraclass correlation coefficient (ICC). Multi‐center reproducibility of traveling volunteers was assessed by a two‐way mixed ICC. The factors age, body mass index, gender and muscle were tested for covariance. ICCs of temporal stability were between 0.963 and 0.999 for all parameters. Water‐T2 relaxation decreased significantly (P < 10^?3) within one hour by ~ 1 ms. Multi‐center reproducibility showed ICCs within 0.879–0.917 with the lowest ICC for mean diffusivity. Different muscles showed the highest covariance, explaining 20–40% of variance for observed parameters. Standardized acquisition and processing of quantitative muscle MRI data resulted in high comparability among centers. The imaging protocol exhibited high temporal stability over one hour except for water T2 relaxation times. These results show that data pooling is feasible and enables assembling data from patients with neuromuscular diseases, paving the way towards larger studies of rare muscle disorders.     

Diffusion‐weighted imaging of normal fibroglandular breast tissue: influence of microperfusion and fat suppression technique on the apparent diffusion coefficient

The influence of microperfusion and fat suppression technique on the apparent diffusion coefficient (ADC) values obtained with diffusion weighted imaging (DWI) of normal fibroglandular breast tissue was investigated. Seven volunteers (14 breasts) were scanned using diffusion weighting factors (b values) up to 1600 s/mm² and the four different fat suppression techniques: STIR, fat saturation, SPAIR, and Water Excitation. The relationship between the logarithmic DW attenuation curves and b was linear for b values up to 600 s/mm² (R² > 0.999). Small differences were noted between the ADC values obtained with the various fat suppression methods, especially at the higher b values. Water Excitation had the highest mean SNR, exceeding STIR (p = 0.03) though not significantly different from fat saturation and SPAIR. In conclusion, the ADC of fibroglandular breast tissue is not influenced by microperfusion and Water Excitation is recommended because it yielded the best SNR values. These factors may be crucial in the differentiation between benign and malignant lesions. Copyright © 2010 John Wiley & Sons, Ltd.     

Tumor apparent diffusion coefficient as an imaging biomarker to predict tumor aggressiveness in patients with estrogen‐receptor‐positive breast cancer

The purpose of this retrospective study was to evaluate whether tumor apparent diffusion coefficient (ADC) was correlated with pathologic biomarkers such as tumor cellularity, Ki67, tumor‐infiltrating lymphocytes (TILs), and peritumoral lymphocytic infiltrate (PLI) in patients with estrogen receptor (ER)‐positive breast cancer. The study was approved by the institutional review board and informed consent was waived. From July 2014 to December 2014, we reviewed 140 ER‐positive tumors in 138 consecutive patients (range, 28–77 years; mean, 52 years) who underwent preoperative breast MRI and definitive surgery. All patients underwent diffusion‐weighted imaging with a 3T scanner. Two radiologists drew the region of interest of the entire tumor and obtained the mean and pixel‐based histogram of ADC. On pathology, two pathologists reviewed tumor cellularity, Ki67, TILs, and PLI. Multiple linear regression analysis was used to determine pathologic variables independently associated with ADC. Tumors with high tumor cellularity and high Ki67 had significantly lower ADCs than those with low tumor cellularity and low Ki67 (P < 0.05 for all). Tumors without PLI had significantly higher standard deviation than those with PLI (0.23 ± 0.08 versus 0.18 ± 0.05; P < 0.001). Median ADC was negatively correlated with tumor cellularity (r = ?0.441), and Ki67 (r = ?0.382). The standard deviation of ADC was also negatively correlated with the degree of PLI (r = ?0.319). On multivariate linear regression analysis, tumor cellularity and Ki67 were independently associated with tumor ADC. Tumor ADC would be an MRI biomarker for the prediction of tumor aggressiveness indicators such as Ki67, tumor cellularity, and PLI in ER‐positive breast cancer. Copyright © 2016 John Wiley & Sons, Ltd.     

Diffusion‐prepared stimulated‐echo turbo spin echo (DPsti‐TSE): An eddy current‐insensitive sequence for three‐dimensional high‐resolution and undistorted diffusion‐weighted imaging

In this study, we present a new three‐dimensional (3D), diffusion‐prepared turbo spin echo sequence based on a stimulated‐echo read‐out (DPsti‐TSE) enabling high‐resolution and undistorted diffusion‐weighted imaging (DWI). A dephasing gradient in the diffusion preparation module and rephasing gradients in the turbo spin echo module create stimulated echoes, which prevent signal loss caused by eddy currents. Near to perfect agreement of apparent diffusion coefficient (ADC) values between DPsti‐TSE and diffusion‐weighted echo planar imaging (DW‐EPI) was demonstrated in both phantom transient signal experiments and phantom imaging experiments. High‐resolution and undistorted DPsti‐TSE was demonstrated in vivo in prostate and carotid vessel wall. 3D whole‐prostate DWI was achieved with four b values in only 6 min. Undistorted ADC maps of the prostate peripheral zone were obtained at low and high imaging resolutions with no change in mean ADC values [(1.60 ± 0.10) × 10^?3 versus (1.60 ± 0.02) × 10^?3 mm²/s]. High‐resolution 3D DWI of the carotid vessel wall was achieved in 12 min, with consistent ADC values [(1.40 ± 0.23) × 10^?3 mm²/s] across different subjects, as well as slice locations through the imaging volume. This study shows that DPsti‐TSE can serve as a robust 3D diffusion‐weighted sequence and is an attractive alternative to the traditional two‐dimensional DW‐EPI approaches.     

Comparison of different MRI sequences in lesion detection and early response evaluation of diffuse large B‐cell lymphoma – a whole‐body MRI and diffusion‐weighted imaging study

To compare different MRI sequences for the detection of lesions and the evaluation of response to chemotherapy in patients with diffuse large B‐cell lymphoma (DLBCL), 18 patients with histology‐confirmed DLBCL underwent 3‐T MRI scanning prior to and 1 week after chemotherapy. The MRI sequences included T₁‐weighted pre‐ and post‐contrast, T₂‐weighted with and without fat suppression, and a single‐shot echo‐planar diffusion‐weighted imaging (DWI) with two b values (0 and 800 s/mm²). Conventional MRI sequence comparisons were performed using the contrast ratio between tumor and normal vertebral body instead of signal intensity. The apparent diffusion coefficient (ADC) of the tumor was measured directly on the parametric ADC map. The tumor volume was used as a reference for the evaluation of chemotherapy response. The mean tumor volume was 374 mL at baseline, and decreased by 65% 1 week after chemotherapy (p < 0.01). The T₂‐weighted image with fat suppression showed a significantly higher contrast ratio compared with images from all other conventional MRI sequences, both before and after treatment (p < 0.01, respectively). The contrast ratio of the T₂‐weighted image with fat suppression decreased significantly (p < 0.01), and that of the T₁‐weighted pre‐contrast image increased significantly (p < 0.01), after treatment. However, there was no correlation between the change in contrast ratio and tumor volume. The mean ADC value was 0.68 × 10^–3 mm²/s at baseline; it increased by 89% after chemotherapy (p < 0.001), and the change in ADC value correlated with the change in tumor volume (r = 0.66, p < 0.01). The baseline ADC value also correlated inversely with the percentage change in ADC after treatment (r = ?0.62, p < 0.01). In conclusion, this study indicates that T₂‐weighted imaging with fat suppression is the best conventional sequence for the detection of lesions and evaluation of the efficacy of chemotherapy in DLBCL. DWI with ADC mapping is an imaging modality with both diagnostic and prognostic value that could complement conventional MRI. Copyright © 2013 John Wiley & Sons, Ltd.     

Multi‐centre reproducibility of diffusion MRI parameters for clinical sequences in the brain

The purpose of this work was to assess the reproducibility of diffusion imaging, and in particular the apparent diffusion coefficient (ADC), intra‐voxel incoherent motion (IVIM) parameters and diffusion tensor imaging (DTI) parameters, across multiple centres using clinically available protocols with limited harmonization between sequences. An ice–water phantom and nine healthy volunteers were scanned across fives centres on eight scanners (four Siemens 1.5T, four Philips 3T). The mean ADC, IVIM parameters (diffusion coefficient D and perfusion fraction f) and DTI parameters (mean diffusivity MD and fractional anisotropy FA), were measured in grey matter, white matter and specific brain sub‐regions. A mixed effect model was used to measure the intra‐ and inter‐scanner coefficient of variation (CV) for each of the five parameters. ADC, D, MD and FA had a good intra‐ and inter‐scanner reproducibility in both grey and white matter, with a CV ranging between 1% and 7.4%; mean 2.6%. Other brain regions also showed high levels of reproducibility except for small structures such as the choroid plexus. The IVIM parameter f had a higher intra‐scanner CV of 8.4% and inter‐scanner CV of 24.8%. No major difference in the inter‐scanner CV for ADC, D, MD and FA was observed when analysing the 1.5T and 3T scanners separately. ADC, D, MD and FA all showed good intra‐scanner reproducibility, with the inter‐scanner reproducibility being comparable or faring slightly worse, suggesting that using data from multiple scanners does not have an adverse effect compared with using data from the same scanner. The IVIM parameter f had a poorer inter‐scanner CV when scanners of different field strengths were combined, and the parameter was also affected by the scan acquisition resolution. This study shows that the majority of diffusion MRI derived parameters are robust across 1.5T and 3T scanners and suitable for use in multi‐centre clinical studies and trials. © 2015 The Authors NMR in Biomedicine Published by John Wiley & Sons Ltd.     

Diffusion‐weighted MRI of the prostate without susceptibility artifacts: Undersampled multi‐shot turbo‐STEAM with rotated radial trajectories

The aim of this study was to develop and evaluate a clinically feasible approach to diffusion‐weighted (DW) MRI of the prostate without susceptibility‐induced artifacts. The proposed method relies on an undersampled multi‐shot DW turbo‐STEAM sequence with rotated radial trajectories and a multi‐step inverse reconstruction with denoised multi‐shot phase maps. The total acquisition time was below 6 min for a resolution of 1.4 × 1.4 × 3.5 mm³ and six directions at b = 600 s mm^?2. Studies of eight healthy subjects and two patients with prostate cancer were performed at 3 T employing an 18‐channel body‐array coil and elements of the spine coil. The method was compared with conventional DW echo‐planar imaging (EPI) of the prostate. The results confirm that DW STEAM MRI avoids geometric distortions and false image intensities, which were present for both single‐shot EPI (ssEPI) and readout‐segmented EPI, particularly near the intestinal wall of the prostate. Quantitative accuracy of the apparent diffusion coefficient (ADC) was validated with use of a numerical phantom providing ground truth. ADC values in the central prostate gland of healthy subjects were consistent with those measured using ssEPI and with literature data. Preliminary results for patients with prostate cancer revealed a correct anatomical localization of lesions with respect to T₂‐weighted MRI in both mean DW STEAM images and ADC maps. In summary, DW STEAM MRI of the prostate offers clinically relevant advantages for the diagnosis of prostate cancer compared with state‐of‐the‐art EPI‐based approaches. The method warrants extended clinical trials.     

Prediction of pathologic response to neoadjuvant chemotherapy in patients with breast cancer using diffusion‐weighted imaging and MRS

The aim of this study was to determine whether tumor size, MRS parameters and apparent diffusion coefficient (ADC) measurements could be applied to predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC). Ninety patients with breast cancer (median size, 4.5 cm; range, 1.6–9.5 cm) were evaluated with single‐voxel ¹H MRS and dynamic contrast‐enhanced MRI. Diffusion‐weighted imaging was performed in 41 of these patients using a 1.5‐T scanner before and after completion of NAC. Pre‐ and post‐treatment measurements and changes in tumor size, MRS parameters [absolute and normalized total choline‐containing compound (tCho) integral and tCho signal‐to‐noise ratio (SNR)] and ADCs in pCR versus non‐pCR were compared using the nonparametric Mann–Whitney test. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic performance of each parameter. After NAC, 30 patients (33%) showed pCR and 60 (67%) showed non‐pCR. At pretreatment, ADC was the only significant parameter in differentiating between pCR and non‐pCR [(0.83 ± 0.05) × 10^–3 versus (0.97 ± 0.14) × 10^–3 mm²/s] (p = 0.014). Post‐treatment measurements after completion of NAC and changes in tumor size (both p < 0.001), MRS parameters (p = 0.027 and p = 0.020 for absolute tCho integral, p = 0.036 and p = 0.023 for normalized tCho integral, and p = 0.032 and p = 0.061 for tCho SNR) and ADC (p = 0.003 and p < 0.001) were significantly different between the pCR and non‐pCR groups, except for changes in tCho SNR. In ROC analysis, the areas under the ROC curve (AUCs) of 0.63–0.73 were obtained for tumor size and MRS parameters. AUCs for pre‐ and post‐treatment ADC and changes in ADC were 0.75, 0.80 and 0.96, respectively. The optimal cut‐off of the percentage change in ADC for predicting pCR was 40.7%, yielding 100% sensitivity and 91% specificity. Patients with pCR showed significantly lower pretreatment ADCs than those with non‐pCR. The change in ADC after NAC was the most accurate predictor of pCR. Copyright © 2012 John Wiley & Sons, Ltd.     

Diffusion‐weighted MRI for staging and evaluation of response in diffuse large B‐cell lymphoma: a pilot study

The aim of this study was to compare diffusion‐weighted MRI (DW‐MRI) with positron emission tomography/computed tomography (PET/CT) for the staging and evaluation of the treatment response in patients with diffuse large B‐cell lymphoma (DLBCL). Institutional review board approval was obtained for this study; all subjects gave informed consent. Twelve patients were imaged before treatment and eight of these were also imaged after two cycles of chemotherapy using both DW‐MRI and PET/CT. Up to six target lesions were selected at baseline for response assessment based on International Working Group criteria (nodes > 1.5 cm in diameter; extranodal lesions > 1 cm in diameter). For pretreatment staging, visual analysis of the numbers of nodal and extranodal lesions based on PET/CT was performed. For interim response assessment after cycle 2 of chemotherapy, residual tumor sites were assessed visually and the percentage changes in target lesion size, maximum standardized uptake value (SUV_max) and apparent diffusion coefficient (ADC) from pretreatment values were calculated. In 12 patients studied pretreatment, there were 46 nodal and 16 extranodal sites of lymphomatous involvement. Agreement between DW‐MRI and PET/CT for overall lesion detection was 97% (60/62 tumor sites; 44/46 nodal and 16/16 extranodal lesions) and, for Ann Arbor stage, it was 100%. In the eight patients who had interim assessment, five of their 49 tumor sites remained abnormal on visual analysis of both DW‐MRI and PET/CT, and there was one false positive on DW‐MRI. Of their 24 target lesions, the mean pretreatment ADC value, tumor size and SUV_max were 772 µm²/s, 21.3 cm² and 16.9 g/mL, respectively. At interim assessment of the same 24 target lesions, ADC values increased by 85%, tumor size decreased by 74% and SUV_max decreased by 83% (all p < 0.01 versus baseline). DW‐MRI provides results comparable with those of PET/CT for staging and early response assessment in patients with DLBCL. Copyright © 2014 John Wiley & Sons, Ltd.     

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 T₂‐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/mm²). 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. Copyright © 2008 John Wiley & Sons, Ltd.     

Determination of the appropriate b value and number of gradient directions for high‐angular‐resolution diffusion‐weighted imaging

High‐angular‐resolution diffusion‐weighted imaging (HARDI) is one of the most common MRI acquisition schemes for use with higher order models of diffusion. However, the optimal b value and number of diffusion‐weighted (DW) directions for HARDI are still undetermined, primarily as a result of the large number of available reconstruction methods and corresponding parameters, making it impossible to identify a single criterion by which to assess performance. In this study, we estimate the minimum number of DW directions and optimal b values required for HARDI by focusing on the angular frequency content of the DW signal itself. The spherical harmonic (SH) series provides the spherical analogue of the Fourier series, and can hence be used to examine the angular frequency content of the DW signal. Using high‐quality data acquired along 500 directions over a range of b values, we estimate that SH terms above l = 8 are negligible in practice for b values up to 5000 s/mm², implying that a minimum of 45 DW directions is sufficient to fully characterise the DW signal. l > 0 SH terms were found to increase as a function of b value, levelling off at b = 3000 s/mm², suggesting that this value already provides the highest achievable angular resolution. In practice, it is recommended to acquire more than the minimum of 45 DW directions to avoid issues with imperfections in the uniformity of the DW gradient directions and to meet signal‐to‐noise requirements of the intended reconstruction method. Copyright © 2013 John Wiley & Sons, Ltd.     

Cytomorphology of male breast lesions: diagnostic pitfalls and clinical implications

Because lesions of the male breast have been exceeded in number by those of the female breast, marginal attention was given to these lesions in the past. Fortunately, this has changed over the years leading to an increased awareness about male breast cancer. Although male breast cancer constitutes only about 1% of all diagnosed breast cancer cases, an increased mortality is seen in this patient population. This is probably caused by late diagnosis as a consequence of low level of concern about breast cancer among male patients. However, the vast majority of lesions of the male breast are benign, gynecomastia being the number one cause of unilateral or bilateral breast mass. Since it is important to avoid unnecessary surgical treatment without missing malignancy, accurate diagnostic tools are necessary in order to triage these patients. Fine-needle aspiration biopsy has demonstrated excellent accuracy in the diagnosis and management of breast lesions in female patients. In addition, several authors have proven the value of this technique in the evaluation of lesions of the male breast. Fine-needle aspiration biopsy permits accurate diagnosis in many lesions arising in the male breast. It also allows gathering cytological material that can be used for ancillary studies which enhances the diagnostic value of this technique.