Tumour subregion analysis of colorectal liver metastases using semi-automated clustering based on DCE-MRI: Comparison with histological subregions and impact on pharmacokinetic parameter analysis.

PURPOSE: To use a novel segmentation methodology based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to define tumour subregions of liver metastases from colorectal cancer (CRC), to compare these with histology, and to use these to compare extracted pharmacokinetic (PK) parameters between tumour subregions. MATERIALS AND METHODS: This ethically-approved prospective study recruited patients with CRC and ≥1 hepatic metastases scheduled for hepatic resection. Patients underwent DCE-MRI pre-metastasectomy. Histological sections of resection specimens were spatially matched to DCE-MRI acquisitions and used to define histological subregions of viable and non-viable tumour. A semi-automated voxel-wise image segmentation algorithm based on the DCE-MRI contrast-uptake curves was used to define imaging subregions of viable and non-viable tumour. Overlap of histologically-defined and imaging subregions was compared using the Dice similarity coefficient (DSC). DCE-MRI PK parameters were compared for the whole tumour and histology-defined and imaging-derived subregions. RESULTS: Fourteen patients were included in the analysis. Direct histological comparison with imaging was possible in nine patients. Mean DSC for viable tumour subregions defined by imaging and histology was 0.738 (range 0.540-0.930). There were significant differences between Ktrans and kep for viable and non-viable subregions (p < 0.001) and between whole lesions and viable subregions (p < 0.001). CONCLUSION: We demonstrate good concordance of viable tumour segmentation based on pre-operative DCE-MRI with a post-operative histological gold-standard. This can be used to extract viable tumour-specific values from quantitative image analysis, and could improve treatment response assessment in clinical practice.

Factors predicting ablation site recurrence following percutaneous microwave ablation of colorectal hepatic metastases.

BACKGROUND: Microwave ablation (MWA) is a recognised treatment option for liver metastases. The size of the tumour is a well-established factor that influences the success of MWA. However, the effect of "heat sink" on the success of MWA for hepatic metastases is unclear. The aim of this study was to determine whether heat sink effect is a factor that contributes to ablation site recurrence (ASR). METHODS: A prospectively maintained database of patients who underwent percutaneous MWA for treatment of colorectal liver metastases was analysed. Imaging and demographic characteristics were compared between metastases that recurred following ablation and those that did not. Proximity to a large hepatic vein was defined as <10 mm. RESULTS: 126 ablations in 87 patients met the inclusion criteria and were studied over a median follow-up period of 28 (12-75) months. ASR was detected in 43 ablations (34%) and was associated with clinical risk score (CRS) ≥2 (OR 2.2 95% CI 1.3-3.3, p = 0.029), metastasis size (OR 0.953 95% CI (0.929-0.978), p < 0.001) and proximity to a large hepatic vein (OR 7.5 95%CI 2.4-22.8, p < 0.001). Proximity to a large hepatic vein was not associated with reduced overall survival (OS) but was associated with liver-specific recurrence (HR 4.7 95%CI 1.7-12.5, p = 0.004). CONCLUSIONS: In addition to tumour size proximity to large hepatic venous structures is an independent predictor of ASR and liver-specific recurrence following MWA. However, this was not associated with overall survival.

Pieces-of-parts for supervoxel segmentation with global context: Application to DCE-MRI tumour delineation.

Rectal tumour segmentation in dynamic contrast-enhanced MRI (DCE-MRI) is a challenging task, and an automated and consistent method would be highly desirable to improve the modelling and prediction of patient outcomes from tissue contrast enhancement characteristics - particularly in routine clinical practice. A framework is developed to automate DCE-MRI tumour segmentation, by introducing: perfusion-supervoxels to over-segment and classify DCE-MRI volumes using the dynamic contrast enhancement characteristics; and the pieces-of-parts graphical model, which adds global (anatomic) constraints that further refine the supervoxel components that comprise the tumour. The framework was evaluated on 23 DCE-MRI scans of patients with rectal adenocarcinomas, and achieved a voxelwise area-under the receiver operating characteristic curve (AUC) of 0.97 compared to expert delineations. Creating a binary tumour segmentation, 21 of the 23 cases were segmented correctly with a median Dice similarity coefficient (DSC) of 0.63, which is close to the inter-rater variability of this challenging task. A second study is also included to demonstrate the method's generalisability and achieved a DSC of 0.71. The framework achieves promising results for the underexplored area of rectal tumour segmentation in DCE-MRI, and the methods have potential to be applied to other DCE-MRI and supervoxel segmentation problems.

Clinical Trial of Oral Nelfinavir before and during Radiation Therapy for Advanced Rectal Cancer.

PURPOSE: Nelfinavir, a PI3K pathway inhibitor, is a radiosensitizer that increases tumor blood flow in preclinical models. We conducted an early-phase study to demonstrate the safety of nelfinavir combined with hypofractionated radiotherapy (RT) and to develop biomarkers of tumor perfusion and radiosensitization for this combinatorial approach. EXPERIMENTAL DESIGN: Ten patients with T3-4 N0-2 M1 rectal cancer received 7 days of oral nelfinavir (1,250 mg b.i.d.) and a further 7 days of nelfinavir during pelvic RT (25 Gy/5 fractions/7 days). Perfusion CT (p-CT) and DCE-MRI scans were performed pretreatment, after 7 days of nelfinavir and prior to the last fraction of RT. Biopsies taken pretreatment and 7 days after the last fraction of RT were analyzed for tumor cell density (TCD). RESULTS: There were 3 drug-related grade 3 adverse events: diarrhea, rash, and lymphopenia. On DCE-MRI, there was a mean 42% increase in medianKtrans, and a corresponding median 30% increase in mean blood flow on p-CT during RT in combination with nelfinavir. Median TCD decreased from 24.3% at baseline to 9.2% in biopsies taken 7 days after RT (P= 0.01). Overall, 5 of 9 evaluable patients exhibited good tumor regression on MRI assessed by tumor regression grade (mrTRG). CONCLUSIONS: This is the first study to evaluate nelfinavir in combination with RT without concurrent chemotherapy. It has shown that nelfinavir-RT is well tolerated and is associated with increased blood flow to rectal tumors. The efficacy of nelfinavir-RT versus RT alone merits clinical evaluation, including measurement of tumor blood flow.

Automated colorectal tumour segmentation in DCE-MRI using supervoxel neighbourhood contrast characteristics.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a powerful protocol for assessing tumour progression from changes in tissue contrast enhancement. Manual colorectal tumour delineation is a challenging and time consuming task due to the complex enhancement patterns in the 4D sequence. There is a need for a consistent approach to colorectal tumour segmentation in DCE-MRI and we propose a novel method based on detection of the tumour from signal enhancement characteristics of homogeneous tumour subregions and their neighbourhoods. Our method successfully detected 20 of 23 cases with a mean Dice score of 0.68 +/- 0.15 compared to expert annotations, which is not significantly different from expert inter-rater variability of 0.73 +/- 0.13 and 0.77 +/- 0.10. In comparison, a standard DCE-MRI tumour segmentation technique, fuzzy c-means, obtained a Dice score of 0.28 +/- 0.17.

Splenic parenchymal heterogeneity at dual-bolus single-acquisition CT in polytrauma patients-6-months experience from Oxford, UK.

Dual-bolus single-acquisition CT (DBSA-CT) has been advocated in the work up of polytrauma cases, providing rapid acquisition and simultaneous visceral and vascular assessment. Splenic heterogeneity has been observed with this technique. The aim of this study was to investigate this phenomenon and assess predisposing factors and impact on image interpretation through a 6-month retrospective audit between March and September 2011. Seventy-three polytrauma patients underwent standardized DBSA-CT. Splenic enhancement was assessed quantitatively using ROIs and image quality using a 5-point visual analog scale; a score of ≥3 was considered diagnostic. Hematoma density was measured in splenic injuries. Age, hemodynamic status, and aortic density were investigated as predictors of splenic heterogeneity. Seventy-three patients were imaged with 98.6 % blunt traumas. There were 5 (6.9 %) splenic injuries. Eight (11 %) had coexisting visceral and vascular injuries.

Hybrid feature-based diffeomorphic registration for tumor tracking in 2-D liver ultrasound images.

Real-time ultrasound image acquisition is a pivotal resource in the medical community, in spite of its limited image quality. This poses challenges to image registration methods, particularly to those driven by intensity values. We address these difficulties in a novel diffeomorphic registration technique for tumor tracking in series of 2-D liver ultrasound. Our method has two main characteristics: 1) each voxel is described by three image features: intensity, local phase, and phase congruency; 2) we compute a set of forces from either local information (Demons-type of forces), or spatial correspondences supplied by a block-matching scheme, from each image feature. A family of update deformation fields which are defined by these forces, and inform upon the local or regional contribution of each image feature are then composed to form the final transformation. The method is diffeomorphic, which ensures the invertibility of deformations. The qualitative and quantitative results yielded by both synthetic and real clinical data show the suitability of our method for the application at hand.

Microwave ablation of pulmonary malignancies using a novel high-energy antenna system.

PURPOSE: To evaluate the technical success, safety, and imaging follow-up of malignant pulmonary nodules treated with a novel high-energy percutaneous microwave ablation (MWA) system. METHODS: Between July 2010 and September 2011, a total of 23 patients, 12 men, mean age 68 (range 30-87) years with 29 pulmonary malignancies of median diameter 19 (range 8-57) mm, underwent computed tomography (CT)-guided MWA with a 16G microwave needle antenna enabling power up to 180 W. Technical success was defined as needle placement in the intended lesion without death or serious injury. Adequacy of ablation was assessed at 24 h on contrast-enhanced CT. Circumferential solid or ground glass opacification >5 mm was used to define an ideal ablation. Local tumor recurrence was assessed at 1, 3, and 6 months after ablation on contrast-enhanced CT. RESULTS: MWA was technically successful in 93 % (n = 27). Mean ablation duration was 3.6 (range 1-9) min. Ten patients (43 %) developed a pneumothorax as a result of the MWA; only 3 (13 %) required placement of a chest drain. Thirty-day mortality rate was 0 %. The mean hospital stay was 1.5 (range 1-7) days. A total of 22 lesions (75 %) were surrounded by ≥5 mm ground glass or solid opacification after the procedure. At a median follow-up of 6 months, local recurrence was identified in 3 out of 26 lesions, giving a local control rate of 88 %. CONCLUSION: MWA using a high-power antenna of pulmonary malignancies is safe, technically achievable, and enables fast ablation times.

The value of true axial imaging for CT staging of colonic cancer.

OBJECTIVE: To assess the effect of true axial computed tomography on the accuracy of staging of colonic cancers. METHOD: Fifty consecutive datasets were independently assessed by three radiologists, experienced in colorectal cancer staging. The first read was of standard axial images only. The second read was 6 weeks later and true axial images, through the tumour and perpendicular to its long axis, were included. RESULTS: The overall accuracy for tumour staging was 56% for reader 1, 48% for reader 2 and 64% for reader 3 for standard axial CT. This improved to 72% (p = 0.012), 66% (p = 0.012) and 80% (p = 0.021) when the true axial images were added. For nodal staging, overall accuracy improved from 56% to 70% (p = 0.065) for reader 1, 58% to 76% (p = 0.012) for reader 2 and 60% to 76% (p = 0.021) for reader 3 between reads. CONCLUSION: The accuracy of CT staging of colonic tumours is significantly improved by reviewing images reconstructed in a plane perpendicular to the long axis of the tumour. The accuracy achieved by this analysis is similar to that of CT colonography but avoids the extra complexity, additional cost and increased complications.