Diffusion MRI: Technical principles and application to uterine cervical cancer.

Imaging is involved in the management of uterine cervical cancer with several objectives: 1/to assess local and lymph node extension of the initial disease; 2/evaluate treatment response to conservative therapy; 3/detect recurrences. Pelvic MRI is the first-line examination in all these indications. It is the key element for delineation after image fusion when the indication of chemoradiation therapy is made. It is also essential for guiding the placement of applicators and optimising the dosimetry of brachytherapy. The diffusion-weighted acquisition is a sequence sensitive to the motion of water molecules. It allows distinguishing water molecules with free diffusion from water molecules with diffusion restricted by obstacles such as cell membranes or the cytoskeleton. The diffusion is thus connected to the cellularity of the explored tissue, and the cancers, being hypercellular, will present a high signal. It thus provides additional information thanks to a high contrast between the tumour and the surrounding tissues, facilitating detection, evaluation of the volume and extent of the disease.

Combining Multiple Magnetic Resonance Imaging Sequences Provides Independent Reproducible Radiomics Features.

To evaluate the relative contribution of different Magnetic Resonance Imaging (MRI) sequences for the extraction of radiomics features in a cohort of patients with lacrimal gland tumors. This prospective study was approved by the Institutional Review Board and signed informed consent was obtained from all participants. From December 2015 to April 2017, 37 patients with lacrimal gland lesions underwent MRI before surgery, including axial T1-WI, axial Diffusion-WI, coronal DIXON-T2-WI and coronal post-contrast DIXON-T1-WI. Two readers manually delineated both lacrimal glands to assess inter-observer reproducibility, and one reader performed two successive delineations to assess intra-observer reproducibility. Radiomics features were extracted using an in-house software to calculate 85 features per region-of-interest (510 features/patient). Reproducible features were defined as features presenting both an intra-class correlation coefficient ≥0.8 and a concordance correlation coefficient ≥0.9 across combinations of the three delineations. Among these features, the ones yielding redundant information were identified as clusters using hierarchical clustering based on the Spearman correlation coefficient. All the MR sequences provided reproducible radiomics features (range 14(16%)-37(44%)) and non-redundant clusters (range 5-14). The highest numbers of features and clusters were provided by the water and in-phase DIXON T2-WI and water and in-phase post-contrast DIXON T1-WI (37, 26, 26 and 26 features and 14,12, 9 and 11 clusters, respectively). A total of 145 reproducible features grouped into 51 independent clusters was provided by pooling all the MR sequences. All MRI sequences provided reproducible radiomics features yielding independent information which could potentially serve as biomarkers.

Radiological evaluation of response to treatment: application to metastatic renal cancers receiving anti-angiogenic treatment.

Targeted therapies have considerably improved the prognosis of patients with metastatic renal cancer (mRCC) but there are no reliable response assessment criteria reflecting the clinical benefits, because there is no regression in size, or it is delayed. Such criteria would help early identification of non-responders, who would then benefit from a change of treatment, and would avoid their being subjected to unnecessary side effects related to the treatment. We will review the imaging techniques currently available for evaluating tumour response in mRCC patients, including the response evaluation criteria in solid tumours (RECIST), the Choi criteria, the modified Choi criteria, and the CT size and attenuation criteria (SACT). We will also discuss functional imaging techniques, which are based on the physiological characteristics of the tumours, such as perfusion CT, magnetic resonance imaging or ultrasound (DCE-CT, DCE-MRI, DCE-US), diffusion MRI, BOLD MRI and new positron emission tomography (PET) tracers. It is not possible at present to propose a unanimously acknowledged criterion for evaluating tumour response to targeted therapy. However, there is a real need for this according to oncologists and the pharmaceutical industry, and radiologists need to be involved in reflecting on the subject.

Shear wave elastography of tumour growth in a human breast cancer model with pathological correlation.

OBJECTIVE: To assess stiffness in a human breast cancer implanted in mice using shear wave elastography (SWE) during tumour growth and to correlate the results with pathology. METHODS: Local ethics committee for animal research approval was obtained. A human invasive ductal carcinoma was implanted subcutaneously in 24 athymic nude female mice. Ultrasound was longitudinally performed in 22 tumours, every 1-2 weeks. Maximum diameter and mean stiffness were collected. Seven tumours were measured both in vivo and ex vivo. Tumours of different sizes were removed for pathological analysis on which the percentages of viable cellular tissue, fibrosis and necrosis were measured. RESULTS: A total of 63 SWE measurements were performed. Stiffness increased during tumour growth with an excellent correlation with size (r = 0.94, P < 0.0001). No differences were found between the values of stiffness in vivo and ex vivo (P = 0.81). There was a significant correlation between elasticity and fibrosis (r = 0.83, P < 0.0001), a negative correlation with necrosis (r = -0.76, p = 0.0004) but no significant correlation with cellular tissue (r = 0.40, p = 0.1). CONCLUSION: Fibrosis plays an important role in stiffness as measured by SWE, whereas necrosis is correlated with softness. KEY POINTS: • In a breast cancer model, ultrasound tumour stiffness is correlated with size. • Stiffness changes with tumour growth are correlated with pathological changes. • Stiffness is very well correlated with proportion of tumour fibrosis. • Stiffness is inversely correlated with proportion of tumour necrosis. • Tumour stiffness measurements are similar in vivo and ex vivo.

[Diffusion-weighted MR imaging of the female pelvis]. / IRM de diffusion et pelvis féminin.

Due to technical advances (parallel imaging and new phased-array coils), diffusion-weighted MR imaging can be used to image the female pelvis. Diffusion-weighted (b=1000) images are now acquired as a complement to conventional sequences (T2W, dynamic T1W images after intravenous injection of gadolinium). Diffusion weighted imaging improves the detection of small uterine tumors and the visualization of small implants of peritoneal carcinomatosis, which could play a significant role for tumor staging. It is helpful for characterization of complex ovarian tumors: the absence of hyperintensity on b=1000 diffusion-weighted images has an excellent positive predictive value for a benign etiology. It could also be helpful to characterize endometrial lesions, to differentiate between endometrial polyp and carcinoma when hysteroscopy is not possible, and to differentiate uterine fibroid from sarcoma. Finally, diffusion-weighted imaging could be helpful to assess the response of uterine tumors to therapy and could confirm a good outcome following uterine artery embolization of uterine fibroids.

Optimizing the size variation threshold for the CT evaluation of response in metastatic renal cell carcinoma treated with sunitinib.

BACKGROUND: In metastatic renal cell carcinoma (mRCC), antiangiogenic treatments rarely achieve a reduction of -30% in the sum of longest diameters (SLD) of target lesions required by RECIST for an 'objective response', although they objectively improve progression-free survival (PFS). We sought to determine a threshold for the computed tomography evaluation of these patients' best reflecting patient outcome. PATIENTS AND METHODS: In 334 mRCC patients treated with sunitinib, we tested thresholds from -45% to +10%. We classified patients as 'responders' when the best relative variation of the sum of longest diameters (DeltaSLD) reached the tested threshold and as 'nonresponders' otherwise. For each tested threshold, the median PFS of the two groups were compared. Receiver operating characteristic (ROC) analysis was also carried out among the 103 patients that progressed during follow-up. Finally, the 'optimal' threshold was retested on an independent cohort of 39 patients. RESULTS: The DeltaSLD threshold of -10% gave the most significant difference. It divided patients into 256 responders and 78 nonresponders (median PFS 11.1 and 5.6 months). The same -10% threshold was found using the ROC analysis. Results were confirmed on the external validation cohort. CONCLUSION: A variation of -10% in the SLD accurately and rapidly identifies mRCC patients benefiting from sunitinib.

[Imaging of response to treatment in oncology]. / Imagerie de la réponse aux traitements en cancérologie.

Imaging plays a crucial role in oncology to assist in the management of patients and selection of drug regimen. Recent advances in imaging techniques allowing to predict and evaluate response to treatments in oncology will be reviewed. The standard in the evaluation of response to treatment is based on the measurement of lesion size. Functional imaging assesses physiological or molecular processes that may be earlier indicators of early response to treatment. Dynamic imaging of tumor vascularization assesses the biodistribution of a contrast agent within tumoral tissues. Diffusion-weighted MR imaging can differentiate free water from water restricted by tissues, providing an assessment of tumor cellularity. MR spectroscopy assesses the relative quantity of specific chemical components within normal and tumoral tissues. 18 FDG PET imaging provides an assessment of the metabolic activity of tissues. FDG uptake is proportional to cellular proliferation and number of viable cells within a tumor. Results from studies assessing the role of these emerging imaging techniques remain preliminary and the medical community must determine their respective role in the routine evaluation of response to treatment in oncological patients.

[Treatment response evaluation by functional imaging]. / Evaluation de la réponse au traitement par imagerie fonctionnelle.

Imaging in cancer plays a capital role to guide the clinician in his choice of therapies. We will discuss the new techniques available to predict and evaluate treatment response in oncology. The method of reference to evaluate treatment response is based on the measure of lesion size. Functional imaging doesn't evaluate size, but rather a physiological or molecular feature, which is probably modified earlier in response to treatment. Dynamic contrast-enhanced functional imaging of microcirculation follows the biodistribution of a contrast agent and analyses tumour vascularization. Diffusion-weighted Magnetic Resonance Imaging differentiates free and restrained water molecules in tissues, reflecting tumor cellularity. Nuclear Magnetic Resonance spectroscopy is an application of MRI that yields information on the metabolic content of a tissue. It detects relative quantities of various molecules which differ in tumour compared to normal tissue. Positon-emission tomography using (18)FDG is a nuclear medicine technique which gives information on tissue metabolism. Captation of FDG is proportional to the proliferative activity and the number of viable cells in a tumour. Human studies concerning these techniques are still quite preliminary, and the medical community must determine their potential in clinical practice to evaluate treatment response in oncology.

[Is mammography useful in Paget's disease of the breast?]. / La mammographie est-elle utile dans la maladie de Paget du sein?

PURPOSE: Interest of the mammogram in Paget's disease of the breast, especially for a therapeutic decision in otherwise asymptomatic women with Paget's disease, who would be candidates for conservative treatment. MATERIALS AND METHODS: 61 women with histological Paget's disease of the nipple, treated by mastectomy, were retrospectively analyzed with clinical, radiological and pathological correlations. RESULTS: An underlying carcinoma was found in 60 cases (98.4%), atypical epithelial hyperplasia in one. In the 24 women without breast palpable mass, 17 (71%) had a normal mammogram, 12 (50%) had carcinoma with an invasive component, 14 (58%) had a cancer at a distance from the nipple, 17 (71%) had a multifocal carcinoma. All 37 women with a palpable mass had a pathological mammogram, 36 of them had carcinoma with an invasive component, 35 (95%) a cancer at a distance from the nipple, 31 (84%) a multifocal carcinoma. CONCLUSION: Mammogram is of limited value in management of Paget's disease of the breast for women without breast palpable mass; it can not predict the site of malignancy, nor the invasive component.