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Open in new tab Download slide Open in new tab Download slide OBJECTIVES Confident growth assessment during imaging follow-up is often limited by substantial variability of diameter measurements and the fact that growth does not always occur at standard measurement locations. There is a need for imaging-based techniques to more accurately assess growth. In this study, we investigated the feasibility of a three-dimensional aortic growth assessment technique to quantify aortic growth in patients following open aortic repair. METHODS Three-dimensional aortic growth was measured using vascular deformation mapping (VDM), a technique which quantifies the localized rate of volumetric growth at the aortic wall, expressed in units of Jacobian (J) per year. We included 16 patients and analysed 6 aortic segments per patient (96 total segments). Growth was assessed by 3 metrics: clinically reported diameters, Jacobian determinant and targeted diameter re-measurements. RESULTS VDM was able to clearly depict the presence or absence of localized aortic growth and allows for an assessment of the distribution of growth and its relation to anatomic landmarks (e.g. anastomoses, branch arteries). Targeted diameter change showed a stronger and significant correlation with J (r  = 0.20, P  = 0.047) compared to clinical diameter change (r  = 0.15, P  = 0.141). Among 20/96 (21%) segments with growth identified by VDM, growth was confirmed by clinical measurements in 7 and targeted re-measurements in 11. Agreement of growth assessments between VDM and diameter measurements was slightly higher for targeted re-measurements (kappa = 0.38) compared to clinical measurements (kappa = 0.25). CONCLUSIONS Aortic growth is often uncertain and underappreciated when assessed via standard diameter measurements. Three-dimensional growth assessment with VDM offers a more comprehensive assessment of growth, allows for targeted diameter measurements and could be an additional tool to determine which post-surgical patients at high and low risk for future complications. [ABSTRACT FROM AUTHOR]

OBJECTIVES Maximal aortic diameter is commonly used to assess aortic risk but poorly predicts the timing and location of dissection events in patients with connective tissue disease who undergo regular imaging surveillance. Hence, we aimed to use available surveillance computed tomography angiography (CTA) scans to investigate the correlation between 3-dimensional (3D) growth and cyclic transmural wall stress with the location of intimal tear formation. METHODS Three type B aortic dissection patients with 2 available electrocardiogram (ECG)-gated pre-dissection CTA scans and without surgical repair during the pre-dissection interval were retrospectively identified at our institution. Vascular deformation mapping was used to measure 3D aortic growth between 2 pre-dissection clinical CTA studies. In addition, we performed a computational analysis to estimate cyclic transmural wall stress in patient-specific baseline CTA geometries. RESULTS In all 3 connective tissue disease patients, the site of type B aortic intimal tear co-localized with areas of peak 3D aortic wall growth. Aortic growth was detected by clinical radiological assessment in only 1 case. Co-localization of peak transmural stress and the site of intimal tear formation were found in all cases. CONCLUSIONS Focal areas of growth and transmural wall stress co-localized with the site of intimal tear formation. These hypothesis-generating results suggest a possible new analytic pathway for a more sophisticated assessment of the factors leading to the initiation of dissection in patients with connective tissue disease. These methods could improve on current risk-stratification techniques. [ABSTRACT FROM AUTHOR]

Head and neck cancer (HNC) is a challenging tumour site for radiotherapy delivery owing to its complex anatomy and proximity to organs at risk (OARs) such as the spinal cord and optic apparatus. Despite significant advances in radiotherapy planning techniques, radiation-induced morbidities remain substantial. Further improvement would require high-quality imaging and tailored radiotherapy based on intratreatment response. For these reasons, the use of MRI in radiotherapy planning for HNC is rapidly gaining popularity. MRI provides superior soft-tissue contrast in comparison with CT, allowing better definition of the tumour and OARs. The lack of additional radiation exposure is another attractive feature for intratreatment monitoring. In addition, advanced MRI techniques such as diffusion-weighted, dynamic contrast-enhanced and intrinsic susceptibility-weighted MRI techniques are capable of characterizing tumour biology further by providing quantitative functional parameters such as tissue cellularity, vascular permeability/perfusion and hypoxia. These functional parameters are known to have radiobiological relevance, which potentially could guide treatment adaptation based on their changes prior to or during radiotherapy. In this article, we first present an overview of the applications of anatomical MRI sequences in head and neck radiotherapy, followed by the potentials and limitations of functional MRI sequences in personalizing therapy. [ABSTRACT FROM AUTHOR]

Objective. In the present study we evaluated the use of four commercially available fluorescent probes to monitor disease activity in murine CIA and its suppression during glucocorticoid therapy. Methods. Arthritis was induced in male DBA/1 mice by immunization with type II collagen in Complete Freund's Adjuvant, followed by a boost of collagen in PBS. Four fluorescent probes from PerkinElmer in combination [ProSense 750 fluorescent activatable sensor technology (FAST) with Neutrophil Elastase 680 FAST and MMPSense 750 FAST with CatK 680 FAST] were used to monitor disease development from day 5 through to day 40 post-immunization. Fluorescence generated in vivo by the probes was correlated with clinical and histological score and paw measurements. Results. The fluorescence intensity emitted by each probe was shown to correlate with the conventional measurements of disease. The highest degree of correlation was observed with ProSense 750 FAST in combination with Neutrophil Elastase 680 FAST; these probes were then used to successfully assess CIA suppression during dexamethasone treatment. Conclusion. We have demonstrated that longitudinal non-invasive duplexed optical fluorescence imaging provides a simple assessment of arthritic disease activity within the joints of mice following the induction of CIA and may represent a powerful tool to monitor the efficacy of drug treatments in preclinical studies. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the serial changes and correlations between readout-segmented technique with navigated phase correction diffusion-weighted MRI (DWI), R2*-MRI and 18F-FDG positron emission tomography (PET) CT performed before and during radiation therapy (RT) in patients with mucosal primary head and neck cancer. Methods: The mean apparent diffusion coefficient (ADCmean) from DWI (at b = 50 and 800 s mm-2), the mean R2* values derived from T2*-MRI, and PET metabolic parameters, including maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV) and total lesional glycolysis (TLG) were measured for the primary tumour. Spearman correlation coefficients were calculated to evaluate correlations between ADCmean, R2*, SUVmax, MTV and TLG. A paired t-test was performed to assess the MRI changes and the slope of serial MRI changes during RT. Results: Pre-treatment scans were performed in 28 patients and mid-treatment scans in 20 patients. No significant correlation was found between ADCmean and either R2* values or PET parameters. There were significant negative correlations of R2* values with pre-treatment PET parameters but not with mid-RT PET parameters: pre-SUVmax (p = 0.008), pre-MTV (p = 0.006) and pre-TLG (p = 0.008). A significant rise in ADCmean was found during the first half (p < 0.001) of RT but not in the second half (p = 0.215) of the treatment. There was an increase of the ADCmean values of 279.4 [95% confidence interval (95% CI): 210-348] in the first half of the treatment (Weeks 0-3). However, during the second-half period of treatment, the mean ADC value (Weeks 3-6) was 24.0 and the 95% CI (-40 to 88) included zero. This suggests that there was no significant change in ADC values during the second half of the treatment. Conclusion: A significant negative correlation was found between pre-treatment R2*-MRI and PET parameters. DWI appeared to demonstrate potentially predictable changes during RT. Advances in knowledge: Understanding the correlation and changes that occur with time between potential imaging biomarkers may help us establish the most appropriate biomarkers to consider in future research. [ABSTRACT FROM AUTHOR]

Objective: To determine the prognostic value of pre-treatment apparent diffusion coefficient (ADC) of colorectal liver metastases in predicting disease response, progression-free survival (PFS) and overall survival (OS). Methods: We retrospectively reviewed 102 patients who underwent pre-treatment diffusion-weighted MRI using a breath-hold (b=0, 150, 500) or a free-breathing (b=0, 50, 100, 250, 500, 750) technique. The mean ADC (b=0-500) and mean flow-insensitive ADC (ADChgh) values (breath- hold: b=150 and 500; free-breathing: b=100 and 500) of up to three hepatic lesions were evaluated in each patient. Clinical and laboratory parameters were recorded. Tumour response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria at 12 weeks after treatment. Associations between tumour response, ADC values and clinical/laboratory parameters were examined by one-way analysis of variance. The relationship of ADC with PFS and OS was determined by Kaplan-Meier analysis. Results: 62 patients responded to chemotherapy at 12 weeks. The pre-treatment mean ADC and mean ADChigh were higher in the non-responding group than in the responding group (1.55 vs 1.36, p=0.033; 1.40 vs 1.16, p=0.024). However, the PFS and OS of the two groups of patients stratified by the median of mean ADC values or threshold derived by receiver operating characteristic analysis were not statis- tically significant. By multivariate Cox regression analysis, patients with ≦2 metastases and response to chemotherapy showed better PFS; white cell count ≦10 and surgical treatment were associated with better OS. Conclusion: Colorectal liver metastasis with higher pre- treatment mean ADC and mean ADChjgh was associated with poorer response to chemotherapy. However, ADC and ADChigh values did not predict the patient outcome in this study cohort. Advances in knowledge: High mean ADC values of colorectal liver metastases on pre-treatment diffusion- weighted MRI is associated with poorer response to chemotherapy. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to determine the prognostic significance of changes in parameters derived from diffusion tensor imaging (DTI) that occur in response to treatment with bevacizumab and irinotecan in patients with recurrent glioblastoma multiforme. Methods: 15 patients with recurrent glioblastoma multiforme underwent serial 1.5 T MRI. Axial single-shot echo planar DTI was obtained on scans performed 3 days and 1 day prior to and 6 weeks after initiation of therapy with bevacizumab and irinotecan. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps were registered to whole brain contrast-enhanced three-dimensional (3D) spoiled gradient recalled and 3D fluid attenuation inversion recovery (FLAIR) image volumes. Anatomic image volumes were segmented to isolate regions of interest defined by tumour-related enhancement (TRE) and FLAIR signal abnormality (FSA). Mean ADC and mean FA were calculated for each region. A Bland-Altman repeatability coefficient was also calculated for each parameter based on the two pre-treatment studies. A patient was considered to have a change in FA or ADC after therapy if the difference between the pre- and post-treatment values was greater than the repeatability coefficient for that parameter. Survival was compared using a Cox proportional hazard model. Results: DTI detected a change in ADC within FSA after therapy in nine patients (five in whom ADC was increased; four in whom it was decreased). Patients with a change in ADC within FSA had significantly shorter overall survival (p=0.032) and progression free survival (p=0.046) than those with no change. Conclusion: In patients with recurrent glioblastoma multiforme treated with bevacizumab and irinotecan, a change in ADC after therapy in FSA is associated with decreased survival. [ABSTRACT FROM AUTHOR]

The frenetic development of imaging technology—both hardware and software—provides exceptional potential for investigation of the lung. In the last two decades, CT was exploited for detailed characterization of pulmonary structures and description of respiratory disease. The introduction of volumetric acquisition allowed increasingly sophisticated analysis of CT data by means of computerized algorithm, namely quantitative CT (QCT). Hundreds of thousands of CTs have been analysed for characterization of focal and diffuse disease of the lung. Several QCT metrics were developed and tested against clinical, functional and prognostic descriptors. Computer-aided detection of nodules, textural analysis of focal lesions, densitometric analysis and airway segmentation in obstructive pulmonary disease and textural analysis in interstitial lung disease are the major chapters of this discipline. The validation of QCT metrics for specific clinical and investigational needs prompted the translation of such metrics from research field to patient care. The present review summarizes the state of the art of QCT in both focal and diffuse lung disease, including a dedicated discussion about application of QCT metrics as parameters for clinical care and outcomes in clinical trials. [ABSTRACT FROM AUTHOR]

Background Prostate cancer is incurable once it has metastasized to the bone. Appropriate preclinical models are lacking. The therapeutic efficacy of the multikinase inhibitor cabozantinib was assessed in an orthotopic xenograft model of castration-resistant prostate cancer (CRPC) bone metastasis using noninvasive, multimodality functional imaging. Methods NOD/SCID mice were injected intratibially with luciferase-expressing ERG (v-ets avian erythroblastosis virus E26 oncogene homolog) rearranged VCaP human prostate carcinoma cells. The response of VCaP xenografts (n = 7 per group) to cabozantinib was investigated using bioluminescence imaging and anatomical and diffusion weighted magnetic resonance imaging. This enabled quantitation of tumor volume and apparent diffusion coefficient (ADC). Bone uptake of technetium-methylene diphosphonate (99mTc-MDP) was assessed by single-photon emission computed tomography. Ex vivo micro computed tomography was used to quantify bone volume and correlated with appropriate histopathology. Statistical significance was determined using the two-sided Mann–Whitney test or Wilcoxon signed rank test. Results VCaP xenografts were predominantly osteosclerotic with some osteolytic activity. Fluorescent in situ hybridization analysis confirmed retention of ERG oncogene rearrangements. Cabozantinib induced a statistically significant 52% reduction in tumor luminance (P = .02) and stasis in tumor volume after 15 days of treatment. Tumor ADC statistically significantly increased with cabozantinib and was associated with extensive necrosis (after 10 days, mean tumor ADC ± SD = 556±43×10−6 mm2/s vs pretreatment ADC = 485±43×10−6 mm2/s; P = .02 ). Tumor-associated uptake of 99mTc-MDP was statistically significantly reduced after 3 days of treatment (P = .02), sustained over 15 days treatment, and associated with a statistically significant (P = .048) reduction in bone growth on the tibial cortex, yet a highly statistically significant (P = .001) increase in trabecular bone volume. Conclusions The intratibial VCaP model faithfully emulates clinical disease. Cabozantinib exerts potent effects on both tumor and tumor-induced bone matrix remodeling, and quantitation of ADC provides a clinically translatable imaging biomarker for early, sensitive assessment of treatment response in CRPC bone metastasis. [ABSTRACT FROM AUTHOR]