ObjectivesTo assess the feasibility of the mono-exponential, bi-exponential and stretched-exponential models in evaluating response of breast tumours to neoadjuvant chemotherapy (NACT) at 3 T.MethodsThirty-six female patients (median age 53, range 32–75 years) with invasive breast cancer undergoing NACT were enrolled for diffusion-weighted MRI (DW-MRI) prior to the start of treatment. For assessment of early response, changes in parameters were evaluated on mid-treatment MRI in 22 patients. DW-MRI was performed using eight b values (0, 30, 60, 90, 120, 300, 600, 900 s/mm2). Apparent diffusion coefficient (ADC), tissue diffusion coefficient (D t), vascular fraction (ƒ), distributed diffusion coefficient (DDC) and alpha (α) parameters were derived. Then t tests compared the baseline and changes in parameters between response groups. Repeatability was assessed at inter- and intraobserver levels.ResultsAll patients underwent baseline MRI whereas 22 lesions were available at mid-treatment. At pretreatment, mean diffusion coefficients demonstrated significant differences between groups (p < 0.05). At mid-treatment, percentage increase in ADC and DDC showed significant differences between responders (49 % and 43 %) and non-responders (21 % and 32 %) (p = 0.03, p = 0.04). Overall, stretched-exponential parameters showed excellent repeatability.ConclusionDW-MRI is sensitive to baseline and early treatment changes in breast cancer using non-mono-exponential models, and the stretched-exponential model can potentially monitor such changes.Key points• Baseline diffusion coefficients demonstrated significant differences between complete pathological responders and non-responders. • Increase in ADC and DDC at mid-treatment can discriminate responders and non-responders. • The ƒ fraction at mid-treatment decreased in responders whereas increased in non-responders. • The mono- and stretched-exponential models showed excellent inter- and intrarater repeatability. • Treatment effects can potentially be assessed by non-mono-exponential diffusion models. Electronic supplementary materialThe online version of this article (doi:10.1007/s00330-016-4630-x) contains supplementary material, which is available to authorized users.
Pressure-volume loops describe dynamic ventricular performance, relevant to patients with and at risk of pulmonary hypertension. We used conductance catheter-derived pressure-volume loops to measure right ventricular (RV) mechanics in patients with chronic thromboembolic pulmonary arterial obstruction at different stages of pathological adaptation. Resting conductance catheterization was performed in 24 patients: 10 with chronic thromboembolic pulmonary hypertension (CTEPH), 7 with chronic thromboembolic disease without pulmonary hypertension (CTED), and 7 controls. To assess the validity of conductance measurements, RV volumes were compared in a subset of 8 patients with contemporaneous cardiac magnetic resonance (CMR). Control, CTED, and CTEPH groups showed different pressure-volume loop morphology, most notable during systolic ejection. Prolonged diastolic relaxation was seen in patients with CTED and CTEPH [tau = 56.2 ± 6.7 (controls) vs. 69.7 ± 10.0 (CTED) vs. 67.9 ± 6.2 ms (CTEPH), P = 0.02]. Control and CTED groups had lower afterload (Ea) and contractility (Ees) compared with the CTEPH group (Ea = 0.30 ± 0.10 vs. 0.52 ± 0.24 vs. 1.92 ± 0.70 mmHg/ml, respectively, P < 0.001) (Ees = 0.44 ± 0.20 vs. 0.59 ± 0.15 vs. 1.13 ± 0.43 mmHg/ml, P < 0.01) with more efficient ventriculoarterial coupling (Ees/Ea = 1.46 ± 0.30 vs. 1.27 ± 0.36 vs. 0.60 ± 0.18, respectively, P < 0.001). Stroke volume assessed by CMR and conductance showed closest agreement (mean bias +9 ml, 95% CI -1 to +19 ml) compared with end-diastolic volume (+48 ml, -16 to 111 ml) and end-systolic volume (+37 ml, -21 to 94 ml). RV conductance catheterization detects novel alteration in pressure-volume loop morphology and delayed RV relaxation in CTED, which distinguish this group from controls. The observed agreement in stroke volume assessed by CMR and conductance suggests RV mechanics are usefully measured by conductance catheter in chronic thromboembolic obstruction.
Hyperpolarised magnetic resonance imaging (HP 13C-MRI) is an emerging clinical technique to detect [1-13C]lactate production in prostate cancer (PCa) following intravenous injection of hyperpolarised [1-13C]pyruvate. Here we differentiate clinically significant PCa from indolent disease in a low/intermediate-risk population by correlating [1-13C]lactate labelling on MRI with the percentage of Gleason pattern 4 (%GP4) disease. Using immunohistochemistry and spatial transcriptomics, we show that HP 13C-MRI predominantly measures metabolism in the epithelial compartment of the tumour, rather than the stroma. MRI-derived tumour [1-13C]lactate labelling correlated with epithelial mRNA expression of the enzyme lactate dehydrogenase (LDHA and LDHB combined), and the ratio of lactate transporter expression between the epithelial and stromal compartments (epithelium-to-stroma MCT4). We observe similar changes in MCT4, LDHA, and LDHB between tumours with primary Gleason patterns 3 and 4 in an independent TCGA cohort. Therefore, HP 13C-MRI can metabolically phenotype clinically significant disease based on underlying metabolic differences in the epithelial and stromal tumour compartments.
Recent concerns over contrast agent safety have encouraged new developments in non-contrast-enhanced vascular imaging techniques. This work investigates the potential for imaging both arteries and veins with vascular anatomy by nonenhanced static subtraction angiography (VANESSA), a method using controllable flow suppression together with subtraction of bright-and dark-blood images. The lower legs of eight healthy volunteers and three patients were imaged using a modified motion-sensitized driven equilibrium preparation, with three-dimensional balanced steady-state free precession readout. The vascular signal decreased with increasing motion-suppression gradient amplitude, and was suppressed when the velocity-encoding parameter was (approximately) less than the measured flow velocity. Selected pairs of images were subtracted to depict vessels with either fast flow (e.g. arteries), slow flow (e.g. veins), or both. Several methodological modifications improved image quality and reduced the background signal from static tissues. Subjectively assessed image quality in volunteers was rated as excellent for 56/64 arterial segments, and good or excellent for 35/64 veins. In conclusion, VANESSA enables rapid noncontrast-enhanced imaging of arteries and veins, combining information on both morphology and flow. This study demonstrates good technical performance in volunteers and evaluation in patients with vascular disease is warranted. Magn Reson Med 67:628-637,
The significant differences in baseline ADCs among primary ovarian cancer, omental cake, and peritoneal deposits indicate that diffusivity profiles may be tumor-site dependent, suggesting biologic heterogeneity of disease. ADC and v(e) parameters correlated with the cytotoxic effects of platinum-based therapy and may be useful response markers, while choline concentration predicted but did not reflect response.
Androgen deprivation therapy (ADT) is a key primary treatment for advanced and metastatic prostate cancer and is an important neoadjuvant before radiotherapy. We evaluated 3.0 T dynamic contrast-enhanced MRI and diffusion-weighted (DW) MRI in monitoring ADT response. Twenty-three consecutive patients with prostate cancer treated by primary ADT were included. Imaging was performed at baseline and 3 months posttreatment with ADT. After 3 months therapy there was a significant reduction in all dynamic contrast-enhanced MRI parameters measured in tumor regions of interest (K trans , k ep , v p , IAUGC-90); P < 0.001. Areas of normal-appearing peripheral zone showed no significant change; P 5 0.285-0.879. Post-ADT, there was no significant change in apparent diffusion coefficient values in tumors, whilst apparent diffusion coefficient values significantly decreased in areas of normalappearing peripheral zone, from 1.786 3 10 23 mm 2 /s to 1.561 3 10 23 mm 2 /s; P 5 0.007. As expected the median ProstateSpecific Antigen (PSA) significantly reduced from 30 ng/mL to 1.5 ng/mL posttreatment, and median prostate volume dropped from 47.6 cm 3 to 24.9 cm 3 ; P < 0.001. These results suggest that dynamic contrast-enhanced MRI and diffusionweighted MRI offer different information but that both could prove useful adjuncts to the anatomical information provided by T2-weighted imaging. dynamic contrast-enhanced as a marker of angiogenesis may help demonstrate ADT resistance and diffusion-weighted imaging may be more accurate in determining presence of tumor cell death versus residual tumor. Magn Reson Med 67:778-785,
ObjectivesTo assess goodness-of-fit and repeatability of mono-exponential, stretched exponential and bi-exponential models of diffusion-weighted MRI (DW-MRI) data in primary and metastatic ovarian cancer.MethodsThirty-nine primary and metastatic lesions from thirty-one patients with stage III or IV ovarian cancer were examined before and after chemotherapy using DW-MRI with ten diffusion-weightings. The data were fitted with (a) a mono-exponential model to give the apparent diffusion coefficient (ADC), (b) a stretched exponential model to give the distributed diffusion coefficient (DDC) and stretching parameter (α), and (c) a bi-exponential model to give the diffusion coefficient (D), perfusion fraction (f) and pseudodiffusion coefficient (D*).ResultsCoefficients of variation, established from repeated baseline measurements, were: ADC 3.1 %, DDC 4.3 %, α 7.0 %, D 13.2 %, f 44.0 %, D* 165.1 %. The bi-exponential model was unsuitable in these data owing to poor repeatability. After excluding the bi-exponential model, analysis using Akaike Information Criteria showed that the stretched exponential model provided the better fit to the majority of pixels in 64 % of lesions.ConclusionsThe stretched exponential model provides the optimal fit to DW-MRI data from ovarian, omental and peritoneal lesions and lymph nodes in pre-treatment and post-treatment measurements with good repeatability.Key points• DW-MRI data in ovarian cancer show deviation from mono-exponential behaviour• Parameters derived from the stretched exponential model showed good repeatability (CV 7 %)• The bi-exponential model was unsuitable because of poor parameter repeatability• The stretched exponential model showed comparable repeatability to the mono-exponential model• The extra parameter (α) provides scope for investigation of heterogeneity or response
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