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Lung imaging is increasingly being used to diagnose, quantify, and phenotype chronic obstructive pulmonary disease (COPD). Although spirometry is the gold standard for the diagnosis of COPD and for severity staging, the role of computed tomography (CT) imaging has expanded in both clinical practice and research. COPD is a heterogeneous disease with considerable variability in clinical features, radiographic disease, progression, and outcomes. Recent studies have examined the utility of CT imaging in enhancing diagnostic certainty, improving phenotyping, predicting disease progression and prognostication, selecting patients for intervention, and also in furthering our understanding of the complex pathophysiology of this disease. Multiple CT metrics show promise for use as imaging biomarkers in COPD. [ABSTRACT FROM AUTHOR]

Lung diseases are increasing in prevalence and overall burden worldwide. To stem the tide, more and more national and international guidelines are recommending the use of various diagnostic algorithms that are disease specific. There is growing consensus among the respiratory community that although patient histories and lung function testing are the minimum required for clinical examinations, these tests alone are not sufficient for disease characterization. Therefore, the use of computed tomography (CT) imaging is increasing used in clinical decision making for lung diseases. Lung diseases affect various components of lung, including the small airways, lung parenchyma, the interstitial space and the pulmonary vasculature. Quantitative CT (QCT) methods are emerging and are increasingly available using commercial software to quantify the underlying disease components, and a growing body of evidence suggests that QCT is an important tool in the clinical setting to help accurately and reproducibly detect where the disease is located in the lung, and to quantify the extent and overall severity for several lung diseases. Furthermore, this growing body of evidence has promoted the use of thoracic QCT to the point that it is now considered by many as an indispensable technology for longitudinal analysis and intervention trials. Many QCT imaging measurements are available to the respiratory physician, and the aim of this review is to introduce and describe pulmonary QCT imaging measurements and methodologies. [ABSTRACT FROM AUTHOR]

State-of-the-art glioma treatment aims to maximise neuro-oncological benefit while minimising losses in quality of life. Optimising this balance remains hindered by our still limited understanding of information processing in the human brain. To help understand individual differences in functional outcomes following neuro-oncological treatment, we review mounting evidence demonstrating the fundamental role that white matter connections play in complex human behaviour. We focus on selected fibre tracts whose destruction is recognised to elicit predictable behavioural deficits and consider specific indications for non-invasive diffusion MRI tractography, the only existing method to map these fibre tracts in vivo, in the selection and planning of neuro-oncological treatments. Despite remaining challenges, longitudinal tract imaging, in combination with intraoperative testing and neuropsychological evaluation, offers unique opportunities to refine our understanding of human brain organisation in the quest to predict and ultimately reduce the quality of life burden of both surgical and non-surgical first-line neuro-oncological therapies. [ABSTRACT FROM AUTHOR]

Purpose Parametric response map (PRM) analysis of functional imaging has been shown to be an effective tool for early prediction of cancer treatment outcomes and may also be well-suited toward guiding personalized adaptive radiotherapy (RT) strategies such as sub-volume boosting. However, the PRM method was primarily designed for analysis of longitudinally acquired pairs of single-parameter image data. The purpose of this study was to demonstrate the feasibility of a generalized parametric response map analysis framework, which enables analysis of multi-parametric data while maintaining the key advantages of the original PRM method. Methods MRI-derived apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) maps acquired at 1 and 3-months post-RT for 19 patients with high-grade glioma were used to demonstrate the algorithm. Images were first co-registered and then standardized using normal tissue image intensity values. Tumor voxels were then plotted in a four-dimensional Cartesian space with coordinate values equal to a voxel's image intensity in each of the image volumes and an origin defined as the multi-parametric mean of normal tissue image intensity values. Voxel positions were orthogonally projected onto a line defined by the origin and a pre-determined response vector. The voxels are subsequently classified as positive, negative or nil, according to whether projected positions along the response vector exceeded a threshold distance from the origin. The response vector was selected by identifying the direction in which the standard deviation of tumor image intensity values was maximally different between responding and non-responding patients within a training dataset. Voxel classifications were visualized via familiar three-class response maps and then the fraction of tumor voxels associated with each of the classes was investigated for predictive utility analogous to the original PRM method. Independent PRM and MPRM analyses of the contrast-enhancing lesion (CEL) and a 1 cm shell of surrounding peri-tumoral tissue were performed. Prediction using tumor volume metrics was also investigated. Leave-one-out cross validation (LOOCV) was used in combination with permutation testing to assess preliminary predictive efficacy and estimate statistically robust P-values. The predictive endpoint was overall survival (OS) greater than or equal to the median OS of 18.2 months. Results Single-parameter PRM and multi-parametric response maps (MPRMs) were generated for each patient and used to predict OS via the LOOCV. Tumor volume metrics ( P ≥ 0.071 ± 0.01) and single-parameter PRM analyses ( P ≥ 0.170 ± 0.01) were not found to be predictive of OS within this study. MPRM analysis of the peri-tumoral region but not the CEL was found to be predictive of OS with a classification sensitivity, specificity and accuracy of 80%, 100%, and 89%, respectively ( P = 0.001 ± 0.01). Conclusions The feasibility of a generalized MPRM analysis framework was demonstrated with improved prediction of overall survival compared to the original single-parameter method when applied to a glioblastoma dataset. The proposed algorithm takes the spatial heterogeneity in multi-parametric response into consideration and enables visualization. MPRM analysis of peri-tumoral regions was shown to have predictive potential supporting further investigation of a larger glioblastoma dataset. [ABSTRACT FROM AUTHOR]

Purpose To develop a continuous-infusion dynamic MRI technique to characterize tumor-associated microvascular proliferation (MVP) in a rat brain model of glioblastoma multiforme. Methods The proposed model assumes effects due to tumor-associated MVP (eg, vascular permeability, Ktrans; intravascular plasma fraction, vp) cannot be individually separated and solves for a single parameter ( kvasc) that quantifies the T1-weighted contrast enhancement from dynamic images acquired during continuous contrast agent (CA) infusion. Untreated C6 tumor-bearing animals ( N = 6) were serially imaged on postoperative days (PODs) 14 and 18 with a 3 Tesla clinical scanner utilizing a dynamic spatial and temporal resolution of 0.38 × 0.38 × 1.5 mm3 and 3.47 s, respectively. Results An association was present between PODs 14 and 18 for median tumor kvasc (Pearson's r = 0.94, P = 0.0052) and CA concentration ([CA], derived from pre- and postcontrast R1 maps; r = 0.94, P = 0.0054). On POD 18, there was a voxel-based association between kvasc and [CA] within each tumor (0.45 < r < 0.82, P < 0.001). However, voxel-based subregions demonstrated a reduced association between kvasc and [CA] ( N = 5; -0.08 < r < 0.22, P > 0.05) or an inverse association ( N = 1; r = -0.28, P = 0.001), indicating differences between locations of vascular permeability and subsequent CA pooling in tumors. Conclusion The continuous-infusion method may provide a quantitative measure for characterizing and monitoring tumor-associated MVP. Magn Reson Med 78:1824-1838, 2017. © 2017 International Society for Magnetic Resonance in Medicine. [ABSTRACT FROM AUTHOR]

Background: Disease accumulates in the small airways without being detected by conventional measurements. Objectives: To quantify small airway disease using a novel computed tomography (CT) inspiratory-to-expiratory approach called the disease probability measure (DPM) and to investigate the association with pulmonary function measurements. Methods: Participants from the population-based CanCOLD study were evaluated using full-inspiration/full-expiration CT and pulmonary function measurements. Full-inspiration and full-expiration CT images were registered, and each voxel was classified as emphysema, gas trapping (GasTrap) related to functional small airway disease, or normal using two classification approaches: parametric response map (PRM) and DPM (VIDA Diagnostics, Inc., Coralville, IA, USA). Results: The participants included never-smokers (n = 135), at risk (n = 97), Global Initiative for Chronic Obstructive Lung Disease I (GOLD I) (n = 140), and GOLD II chronic obstructive pulmonary disease (n = 96). PRMGasTrap and DPMGasTrap measurements were significantly elevated in GOLD II compared to never-smokers (p < 0.01) and at risk (p < 0.01), and for GOLD I compared to at risk (p < 0.05). Gas trapping measurements were significantly elevated in GOLD II compared to GOLD I (p < 0.0001) using the DPM classification only. Overall, DPM classified significantly more voxels as gas trapping than PRM (p < 0.0001); a spatial comparison revealed that the expiratory CT Hounsfield units (HU) for voxels classified as DPMGasTrap but PRMNormal (PRMNormal- DPMGasTrap = -785 ± 72 HU) were significantly reduced compared to voxels classified normal by both approaches (PRMNormal-DPMNormal = --722 ± 89 HU; p < 0.0001). DPM and PRM GasTrap measurements showed similar, significantly associations with forced expiratory volume in 1 s (FEV1) (p < 0.01), FEV1/forced vital capacity (p < 0.0001), residual volume/total lung capacity (p < 0.0001), bronchodilator response (p < 0.0001), and dyspnea (p < 0.05). Conclusion: CT inspiratory-to-expiratory gas trapping measurements are significantly associated with pulmonary function and symptoms. There are quantitative and spatial differences between PRM and DPM classification that need pathological investigation. [ABSTRACT FROM AUTHOR]

Increasing use of novel systemic treatment options in the management of patients with advanced hepatocellular carcinoma (HCC) such as antiangiogenic and molecular-targeted therapies, poses unique challenges for effective treatment monitoring and efficacy assessment. The traditional morphological criteria such as response evaluation criteria in solid tumor (RECIST) rely on changes in tumor size to determine treatment efficacy. However, these criteria based on tumor morphology may not be suitable to monitor response to newer targeted therapies as early functional changes induced by these drugs precede changes in tumor size. Modifications of these morphological criteria that determine response based on tumor enhancement characteristics such asmodified RECIST (mRECIST) will potentially allow improved determination of treatment response pending validation from prospective trials. Advanced functional imaging techniques such as perfusion imaging (computed tomography/magnetic resonance imaging [CT/MRI]), diffusion weighted MRI (DW-MRI) and positron emission tomography (PET/CT and PET/MRI) are being increasingly used as surrogate imaging biomarkers to provide superior assessment of changes in tumor physiology. Growing emphasis on precision oncological care tailored to specific tumor type and individual patients renders the use of these newer imaging modalities more pertinent and timely. In this review, the authors discuss the role of various imaging techniques and response assessment criteria in the evaluation of systemic therapy for advanced HCC with focus on functional imaging tools. [ABSTRACT FROM AUTHOR]

Objectives: To correlate early changes in the parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) within 1 week of systemic therapy with overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC).Methods: Eighty-nine patients with advanced HCC underwent DCE-MRI before and within 1 week following systemic therapy. The relative changes of six DCE-MRI parameters (Peak, Slope, AUC, Ktrans, Kep and Ve) of the tumours were correlated with OS using the Kaplan-Meier model and the double-sided log-rank test.Results: All patients died and the median survival was 174 days. Among the six DCE-MRI parameters, reductions in Peak, AUC, and Ktrans, were significantly correlated with one another. In addition, patients with a high Peak reduction following treatment had longer OS (P = 0.023) compared with those with a low Peak reduction. In multivariate analysis, a high Peak reduction was an independent favourable prognostic factor in all patients [hazard ratio (HR), 0.622; P = 0.038] after controlling for age, sex, treatment methods, tumour size and stage, and Eastern Cooperative Oncology Group performance status.Conclusions: Early perfusion changes within 1 week following systemic therapy measured by DCE-MRI may aid in the prediction of the clinical outcome in patients with advanced HCC.Key Points: • DCE-MRI is helpful to evaluate perfusion changes of HCC after systemic treatment. • Early perfusion changes within 1 week after treatment may predict overall survival. • High Peak reduction was an independent favourable prognostic factor after systemic treatment. [ABSTRACT FROM AUTHOR]

Purpose A temporal diffusion MRI spectroscopy based approach has been developed to quantify cancer cell size and density in vivo. Methods A novel imaging microstructural parameters using limited spectrally edited diffusion (IMPULSED) method selects a specific limited diffusion spectral window for an accurate quantification of cell sizes ranging from 10 to 20 μm in common solid tumors. In practice, it is achieved by a combination of a single long diffusion time pulsed gradient spin echo (PGSE) and three low-frequency oscillating gradient spin echo (OGSE) acquisitions. To validate our approach, hematoxylin and eosin staining and immunostaining of cell membranes, in concert with whole slide imaging, were used to visualize nuclei and cell boundaries, and hence, enabled accurate estimates of cell size and cellularity. Results Based on a two compartment model (incorporating intra- and extracellular spaces), accurate estimates of cell sizes were obtained in vivo for three types of human colon cancers. The IMPULSED-derived apparent cellularities showed a stronger correlation (r = 0.81; P < 0.0001) with histology-derived cellularities than conventional ADCs (r = −0.69; P < 0.03). Conclusion The IMPULSED approach samples a specific region of temporal diffusion spectra with enhanced sensitivity to length scales of 10-20 μm, and enables measurements of cell sizes and cellularities in solid tumors in vivo. Magn Reson Med 78:156-164, 2017. © 2016 International Society for Magnetic Resonance in Medicine [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the prognostic significance of parametric response mapping (PRM) analysis for hepatocellular carcinoma (HCC) patients undergoing transarterial chemoembolization (TACE). Methods: We recruited 65 HCC patients who underwent TACE. These patients underwent longitudinal multiphasic CT before and after TACE. We applied PRM analysis to the baseline CT before TACE and first/second follow-up CTs. The results of PRM analyses were used to stratify patients into responders and non-responders. Overall survival was compared between the two groups. An independent survival analysis using conventional radiological assessments was performed, and the results were compared with PRM results. Univariate and multivariate analyses were performed to identify clinical factors affecting survival. Results: The PRM analyses demonstrated that the responding group had a median survival of 529 days, while the non-responding group had a median survival of 263 days [hazard ratio (HR) 12.9, p < 0.05 for differences in survival]. The manual analyses indicated median survivals of 491 and 329 days for the responding and non-responding groups, respectively (HR 2.7, p < 0.05). Tumor size, albumin level, and PRM values were found to be significantly related to overall survival after univariate and multivariate analyses. Conclusions: The PRM analysis could be a better predictor of overall survival for patients with HCC undergoing TACE than conventional radiological assessments. [ABSTRACT FROM AUTHOR]

Background: Novel advanced MRI techniques are investigated in patients treated for head and neck tumors as conventional anatomical MRI is unreliable to differentiate tumor from treatment related imaging changes. Purpose: As the diagnostic accuracy of MRI techniques to detect tumor residual or recurrence during or after treatment is variable reported in the literature, we performed a systematic meta-analysis. Data sources: Pubmed, EMBASE and Web of Science were searched from their first record to September 23th 2014. Study selection: Studies reporting diagnostic accuracy of anatomical, ADC, perfusion or spectroscopy to identify tumor response confirmed by histology or follow-up in treated patients for head and neck tumors were selected by two authors independently. Data analysis: Two authors independently performed data extraction including true positives, false positives, true negatives, false negatives and general study characteristics. Meta-analysis was performed using bivariate random effect models when ≥5 studies per test were included. Data synthesis: We identified 16 relevant studies with anatomical MRI and ADC. No perfusion or spectroscopy studies were identified. Pooled analysis of anatomical MRI of the primary site (11 studies, N = 854) displayed a sensitivity of 84% (95%CI 72–92) and specificity of 82% (71–89). ADC of the primary site (6 studies, N = 287) showed a pooled sensitivity of 89% (74–96) and specificity of 86% (69–94). Limitations: Main limitation are the low, but comparable quality of the included studies and the variability between the studies. Conclusions: The higher diagnostic accuracy of ADC values over anatomical MRI for the primary tumor location emphases the relevance to include DWI with ADC for response evaluation of treated head and neck tumor patients. [ABSTRACT FROM AUTHOR]

The hypothesis that the small conducting airways were the major site of obstruction to airflow in normal lungs was introduced by Rohrer in 1915 and prevailed until Weibel introduced a quantitative method of studying lung anatomy in 1963. Green repeated Rohrer's calculations using Weibels new data in 1965 and found that the smaller conducting airways offered very little resistance to airflow. This conflict was resolved by seminal experiments conducted by Macklem and Mead in 1967, which confirmed that a small proportion of the total lower airways resistance is attributable to small airways<2mmin diameter. Shortly thereafter, Hogg, Macklem, and Thurlbeck used this technique to show that small airways become the major site of obstruction in lungs affected by emphysema. These and other observations led Mead to write a seminal editorial in 1970 that postulated the small airways are a silent zone within normal lungs where disease can accumulate over many years without being noticed. This review provides a progress report since the 1970s on methods for detecting chronic obstructive pulmonary disease, the structural nature of small airways' disease, and the cellular and molecular mechanisms that are thought to underlie its pathogenesis. [ABSTRACT FROM AUTHOR]

Rationale: The predominant cause of chronic lung allograft failure is small airway obstruction arising from bronchiolitis obliterans. However, clinical methodologies for evaluating presence and degree of small airway disease are lacking.Objectives: To determine if parametric response mapping (PRM), a novel computed tomography voxel-wise methodology, can offer insight into chronic allograft failure phenotypes and provide prognostic information following spirometric decline.Methods: PRM-based computed tomography metrics quantifying functional small airways disease (PRMfSAD) and parenchymal disease (PRMPD) were compared between bilateral lung transplant recipients with irreversible spirometric decline and control subjects matched by time post-transplant (n = 22). PRMfSAD at spirometric decline was evaluated as a prognostic marker for mortality in a cohort study via multivariable restricted mean models (n = 52).Measurements and Main Results: Patients presenting with an isolated decline in FEV1 (FEV1 First) had significantly higher PRMfSAD than control subjects (28% vs. 15%; P = 0.005), whereas patients with concurrent decline in FEV1 and FVC had significantly higher PRMPD than control subjects (39% vs. 20%; P = 0.02). Over 8.3 years of follow-up, FEV1 First patients with PRMfSAD greater than or equal to 30% at spirometric decline lived on average 2.6 years less than those with PRMfSAD less than 30% (P = 0.004). In this group, PRMfSAD greater than or equal to 30% was the strongest predictor of survival in a multivariable model including bronchiolitis obliterans syndrome grade and baseline FEV1% predicted (P = 0.04).Conclusions: PRM is a novel imaging tool for lung transplant recipients presenting with spirometric decline. Quantifying underlying small airway obstruction via PRMfSAD helps further stratify the risk of death in patients with diverse spirometric decline patterns. [ABSTRACT FROM AUTHOR]

The safety and efficacy of chemotherapeutics can vary as a function of the time of their delivery during the day. This study aimed to improve the treatment of glioblastoma (GBM), the most common brain cancer, by testing whether the efficacy of the DNA alkylator temozolomide (TMZ) varies with the time of its administration. We found cell-intrinsic, daily rhythms in both human and mouse GBM cells. Circadian time of treatment affected TMZ sensitivity of murine GBM tumor cells in vitro. The maximum TMZ-induced DNA damage response, activation of apoptosis, and growth inhibition occurred near the daily peak in expression of the core clock gene Bmal1. Deletion of Bmal1 (Arntl) abolished circadian rhythms in gene expression and TMZ-induced activation of apoptosis and growth inhibition. These data indicate that tumor cell-intrinsic circadian rhythms are common to GBM tumors and can regulate TMZ cytotoxicity. Optimization of GBM treatment by timing TMZ administration to daily rhythms should be evaluated in prospective clinical trials. [ABSTRACT FROM AUTHOR]

Rationale: Very little is known about airways that are too small to be visible on thoracic multidetector computed tomography but larger than the terminal bronchioles.Objectives: To examine the structure of preterminal bronchioles located one generation proximal to terminal bronchioles in centrilobular and panlobular emphysema.Methods: Preterminal bronchioles were identified by backtracking from the terminal bronchioles, and their centerlines were established along the entire length of their lumens. Multiple cross-sectional images perpendicular to the centerline were reconstructed to evaluate the bronchiolar wall and lumen, and the alveolar attachments to the outer airway walls in relation to emphysematous destruction in 28 lung samples from six patients with centrilobular emphysema, 20 lung samples from seven patients with panlobular emphysema associated with alpha-1 antitrypsin deficiency, and 47 samples from seven control (donor) lungs.Measurements and Main Results: The preterminal bronchiolar length, wall volume, total volume (wall + lumen), lumen circularity, and number of alveolar attachments were reduced in both centrilobular and panlobular emphysema compared with control lungs. In contrast, thickening of the wall and narrowing of the lumen were more severe and heterogeneous in centrilobular than in panlobular emphysema. The bronchiolar lumen was narrower in the middle than at both ends, and the decreased number of alveolar attachments was associated with increased wall thickness in centrilobular emphysema.Conclusions: These results provide new information about small airways pathology in centrilobular and panlobular emphysema and show that these changes affect airways that are not visible with thoracic multidetector computed tomography scans but located proximal to the terminal bronchioles in chronic obstructive pulmonary disease. [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]

Rationale: Aging is associated with reduced FEV1 to FVC ratio (FEV1/FVC), hyperinflation, and alveolar enlargement, but little is known about how age affects small airways.Objectives: To determine if chest computed tomography (CT)-assessed functional small airway would increase with age, even among asymptomatic individuals.Methods: We used parametric response mapping analysis of paired inspiratory/expiratory CTs to identify functional small airway abnormality (PRMFSA) and emphysema (PRMEMPH) in the SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) cohort. Using adjusted linear regression models, we analyzed associations between PRMFSA and age in subjects with or without airflow obstruction. We subdivided participants with normal spirometry based on respiratory-related impairment (6-minute-walk distance <350 m, modified Medical Research Council ≥2, chronic bronchitis, St. George's Respiratory Questionnaire >25, respiratory events requiring treatment [antibiotics and/or steroids or hospitalization] in the year before enrollment).Measurements and Main Results: Among 580 never- and ever-smokers without obstruction or respiratory impairment, PRMFSA increased 2.7% per decade, ranging from 3.6% (ages 40-50 yr) to 12.7% (ages 70-80 yr). PRMEMPH increased nonsignificantly (0.1% [ages 40-50 yr] to 0.4% [ages 70-80 yr]; P = 0.34). Associations were similar among nonobstructed individuals with respiratory-related impairment. Increasing PRMFSA in subjects without airflow obstruction was associated with increased FVC (P = 0.004) but unchanged FEV1 (P = 0.94), yielding lower FEV1/FVC ratios (P < 0.001). Although emphysema was also significantly associated with lower FEV1/FVC (P = 0.04), its contribution relative to PRMFSA in those without airflow obstruction was limited by its low burden.Conclusions: In never- and ever-smokers without airflow obstruction, aging is associated with increased FVC and CT-defined functional small airway abnormality regardless of respiratory symptoms. [ABSTRACT FROM AUTHOR]

Advanced radiotherapy techniques, such as intensity-modulated radiotherapy, have been reported to reduce toxicities by improving the dose conformity in mucosal primary head and neck cancer (MPHNC). However, to further optimize the therapeutic ratio, details on individual patient and disease characteristics may be necessary to tailor treatments. This is likely to include identifying poor responders for treatment intensification and good responders for de-escalation strategies. Non-invasive, repeatable imaging biomarkers are attractive modalities in both pre-treatment and intra-treatment response prediction with a view to individualized treatment options. This review has assessed the current literature on the prognostic/predictive role of widely available functional imaging (FI) studies such as fMRI(functional magnetic resonance imaging), functional computed tomography (fCT) and positron-emission-tomography(PET). A literature search was carried out using Medline, Embase and PubMed. Studies were included if imaging was undertaken pre and/or during radiotherapy (with or without the addition of chemotherapy and/or surgery). A total of 99 relevant studies were identified: 14 fMRI, 10 fCT, 59 FDG-PET and 16 non-FDG-PET studies. These articles were reviewed to identify imaging parameters demonstrating a correlation with patient outcome or a factor considered to impact on patient outcome and thus likely to be of potential predictive value in MPHNC and associated future radiotherapy treatment directions. Several studies have demonstrated that both pre-treatment and mid-treatment FDG-PET is predictive of outcomes. However, further studies are required to confirm the role of other imaging studies including fMRI and PET using other tracers. There is large heterogeneity within and between published studies, including tumour sites, treatment options, outcome endpoints and parameters assessed. We propose a minimum set of factors that should be reported and make recommendations for studies evaluating the predictive utility in MPHNC. [ABSTRACT FROM AUTHOR]

Background: Boron neutron capture therapy (BNCT) is a unique particle radiation therapy based on the nuclear capture reactions in boron-10. We developed a novel boron-10 containing sodium borocaptate (BSH) derivative, 1-amino-3-fluorocyclobutane-1-carboxylic acid (ACBC)-BSH. ACBC is a tumor selective synthetic amino acid. The purpose of this study was to assess the biodistribution of ACBC-BSH and its therapeutic efficacy following Boron Neutron Capture Therapy (BNCT) of the F98 rat glioma.Methods: We evaluated the biodistribution of three boron-10 compounds, ACBC-BSH, BSH and boronophenylalanine (BPA), in vitro and in vivo, following intravenous (i.v.) administration and intratumoral (i.t.) convection-enhanced delivery (CED) in F98 rat glioma bearing rats. For BNCT studies, rats were stratified into five groups: untreated controls, neutron-irradiation controls, BNCT with BPA/i.v., BNCT with ACBC-BSH/CED, and BNCT concomitantly using BPA/i.v. and ACBC-BSH/CED.Results: In vitro, ACBC-BSH attained higher cellular uptake F98 rat glioma cells compared with BSH. In vivo biodistribution studies following i.v. administration and i.t. CED of ACBC-BSH attained significantly higher boron concentrations than that of BSH, but much lower than that of BPA. However, following convection enhanced delivery (CED), ACBC-BSH attained significantly higher tumor concentrations than BPA. The i.t. boron-10 concentrations were almost equal between the ACBC-BSH/CED group and BPA/i.v. group of rats. The tumor/brain boron-10 concentration ratio was higher with ACBC-BSH/CED than that of BPA/i.v. group. Based on these data, BNCT studies were carried out in F98 glioma bearing rats using BPA/i.v. and ACBC-BSH/CED as the delivery agents. The corresponding mean survival times were 37.4 ± 2.6d and 44.3 ± 8.0d, respectively, and although modest, these differences were statistically significant.Conclusions: Our findings suggest that further studies are warranted to evaluate ACBC-BSH/CED as a boron delivery agent. [ABSTRACT FROM AUTHOR]

Copyright of Progress in Modern Biomedicine is the property of Publishing House of Progress in Modern Biomedicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: There is an increasing need for small animal in vivo imaging in murine orthotopic glioma models. Because dedicated small animal scanners are not available ubiquitously, the applicability of a clinical CT scanner for visualization and measurement of intracerebrally growing glioma xenografts in living mice was validated. Materials and Methods: 2.5x106 U87MG cells were orthotopically implanted in NOD/SCID/ᵞc-/- mice (n = 9). Mice underwent contrast-enhanced (300 μl Iomeprol i.v.) imaging using a micro-CT (80 kV, 75 μAs, 360° rotation, 1,000 projections, scan time 33 s, resolution 40 x 40 x 53 μm) and a clinical CT scanner (4-row multislice detector; 120 kV, 150 mAs, slice thickness 0.5 mm, feed rotation 0.5 mm, resolution 98 x 98 x 500 μm). Mice were sacrificed and the brain was worked up histologically. In all modalities tumor volume was measured by two independent readers. Contrast-to-noise ratio (CNR) and Signal-to-noise ratio (SNR) were measured from reconstructed CT-scans (0.5 mm slice thickness; n = 18). Results: Tumor volumes (mean±SD mm3) were similar between both CT-modalities (micro-CT: 19.8±19.0, clinical CT: 19.8±18.8; Wilcoxon signed-rank test p = 0.813). Moreover, between reader analyses for each modality showed excellent agreement as demonstrated by correlation analysis (Spearman-Rho >0.9; p<0.01 for all correlations). Histologically measured tumor volumes (11.0±11.2) were significantly smaller due to shrinkage artifacts (p<0.05). CNR and SNR were 2.1±1.0 and 1.1±0.04 for micro-CT and 23.1±24.0 and 1.9±0.7 for the clinical CTscanner, respectively. Conclusion: Clinical CT scanners may reliably be used for in vivo imaging and volumetric analysis of brain tumor growth in mice. [ABSTRACT FROM AUTHOR]

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Rationale: The small conducting airways are the major site of airflow obstruction in chronic obstructive pulmonary disease and may precede emphysema development.Objectives: We hypothesized a novel computed tomography (CT) biomarker of small airway disease predicts FEV1 decline.Methods: We analyzed 1,508 current and former smokers from COPDGene with linear regression to assess predictors of change in FEV1 (ml/yr) over 5 years. Separate models for subjects without and with airflow obstruction were generated using baseline clinical and physiologic predictors in addition to two novel CT metrics created by parametric response mapping (PRM), a technique pairing inspiratory and expiratory CT images to define emphysema (PRM(emph)) and functional small airways disease (PRM(fSAD)), a measure of nonemphysematous air trapping.Measurements and Main Results: Mean (SD) rate of FEV1 decline in ml/yr for GOLD (Global Initiative for Chronic Obstructive Lung Disease) 0-4 was as follows: 41.8 (47.7), 53.8 (57.1), 45.6 (61.1), 31.6 (43.6), and 5.1 (35.8), respectively (trend test for grades 1-4; P < 0.001). In multivariable linear regression, for participants without airflow obstruction, PRM(fSAD) but not PRM(emph) was associated with FEV1 decline (P < 0.001). In GOLD 1-4 participants, both PRM(fSAD) and PRM(emph) were associated with FEV1 decline (P < 0.001 and P = 0.001, respectively). Based on the model, the proportional contribution of the two CT metrics to FEV1 decline, relative to each other, was 87% versus 13% and 68% versus 32% for PRM(fSAD) and PRM(emph) in GOLD 1/2 and 3/4, respectively.Conclusions: CT-assessed functional small airway disease and emphysema are associated with FEV1 decline, but the association with functional small airway disease has greatest importance in mild-to-moderate stage chronic obstructive pulmonary disease where the rate of FEV1 decline is the greatest. Clinical trial registered with www.clinicaltrials.gov (NCT 00608764). [ABSTRACT FROM AUTHOR]

Objectives: To assess the utility of diffusion weighted imaging for monitoring early treatment effects associated with a VEGF inhibitor.Materials and Methods: Twenty-nine patients with metastatic abdominal and pelvic tumours were recruited and imaged with DW-MRI: twice at baseline, and after 7 and 28 days of treatment with cediranib. Tumour measures were derived using mono-exponential, bi-exponential and stretched-exponential models, and parameter repeatability and treatment effects seen after 7 and 28 days were assessed. Correlations with volume changes and DCE-MRI metrics were also assessed.Results: Diffusion coefficient repeatabilities from all models were < 6%; f and D* (bi-exponential) were 22% and 44%; α (stretched-exponential) was 4.2%. Significant increases in the diffusion coefficients from all models were observed at day 28 but not day 7. Significant decreases in D* and f.D* were observed at day 7 and in f at day 28; significant increases in α were observed at both time-points. Weak correlations between DW-MRI changes and volume changes and DCE-MRI changes were observed.Conclusion: DW-MRI is sensitive to early and late treatment changes caused by a VEGF inhibitor using non-mono-exponential models. Evidence of over-fitting using the bi-exponential model suggests that the stretched-exponential model is best suited to monitor such changes.Key Points: • Non-mono-exponential diffusion models widen sensitivity to a broader class of tissue properties. • A stretched-exponential model robustly detects changes after 7 days of VEGF-inhibitor treatment. • There are very weak correlations between DWI-IVIM perfusion and similar DCE-MRI measures. • Diffusion-weighted MRI is a highly informative technique for assessing novel tumour therapies. [ABSTRACT FROM AUTHOR]

The RAS genes encode for members of a large superfamily of guanosine-5′-triphosphate (GTP)-binding proteins that control diverse intracellular signaling pathways to promote cell proliferation. Somatic mutations in the RAS oncogenes are the most common activating lesions found in human cancers. These mutations invariably result in the gain-of-function of RAS by impairing GTP hydrolysis and are frequently associated with poor responses to standard cancer therapies. In this review, we summarize key findings of past and present landmark studies that have deepened our understanding of the RAS biology in the context of oncogenesis. We also discuss how emerging areas of research could further bolster a renewed global effort to target the largely undruggable oncogenic RAS and/or its activated downstream effector signaling cascades to achieve better treatment outcomes for RAS-mutant cancer patients. [ABSTRACT FROM AUTHOR]

The purpose of our study was to investigate the therapeutic efficacy of intraarterial (IA) chemotherapy via multiparametric magnetic resonance imaging (MRI) analysis in orthotopic mouse brain tumor models. Stereotactic-guided intracranial inoculation of MDA-MB-231 cells was performed in nude mice. Thirty tumor bearing mice were randomized into three groups, and each group received either IA docetaxel administration ( n = 10), intravenous (IV) docetaxel administration ( n = 10), or IA solvent injection ( n = 10) as control. Treatment response was monitored by diffusion-weighted imaging and dynamic contrast enhanced-MRI obtained 1 day before and 8 days after therapy initiation. Imaging results were correlated with histopathology. In the results, IA chemotherapy showed a significant decrease in tumor volume (86.5 ± 15.6 %) compared to the IV chemotherapy (121.1 ± 39.6 %) and control (126.2 ± 22.0 %) 8 days after therapy ( p < 0.05). Furthermore, IA chemotherapy resulted in a significant increase in mean tumor apparent diffusion coefficient (ADC) values (116.8 ± 44.9 %); in contrary IV chemotherapy (66.6 ± 26.9 %) and control (69.1 ± 29.5 %) showed a significant decrease in ADC values corresponding to further tumor growth ( p < 0.05). However, there was no significant difference in perfusion parameters including initial area under the curve, K, K, and V between the groups ( p > 0.05). Histopathology confirmed necrosis and necroptosis in the tumors after IA chemotherapy. In conclusion, IA chemotherapy may lead to effective inhibition of tumor cell proliferation and offer potential benefit of inducing higher degree of treatment response than IV chemotherapy. [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]

The goal of this study was to develop a 3D diffusion weighted sequence for free breathing liver imaging in small animals at high magnetic field. Hepatic metastases were detected and the apparent diffusion coefficients (ADC) were measured. A 3D SE-EPI sequence was developed by (i) inserting a water-selective excitation radiofrequency pulse to suppress adipose tissue signal and (ii) bipolar diffusion gradients to decrease the sensitivity to respiration motion. Mice with hepatic metastases were imaged at 7T by applying b values from 200 to 1100 s/mm. 3D images with high spatial resolution (182 × 156 × 125 µm) were obtained in only 8 min 32 s. The modified DW-SE-EPI sequence allowed to obtain 3D abdominal images of healthy mice with fat SNR 2.5 times lower than without any fat suppression method and sharpness 2.8 times higher than on respiration-triggered images. Due to the high spatial resolution, the core and the periphery of disseminated hepatic metastases were differentiated at high b-values only, demonstrating the presence of edema and proliferating cells (with ADC of 2.65 × 10 and 1.55 × 10 mm/s, respectively). Furthermore, these metastases were accurately distinguished from proliferating ones within the same animal at high b-values (mean ADC of 0.38 × 10 mm/s). Metastases of less than 1.7 mm diameter were detected. The new 3D SE-EPI sequence enabled to obtain diffusion information within liver metastases. In addition of intra-metastasis heterogeneity, differences in diffusion were measured between metastases within an animal. This sequence could be used to obtain diffusion information at high magnetic field. [ABSTRACT FROM AUTHOR]

High magnetic fields expand our capability to use sodium MRI for biomedical applications. The central goal of this review is devoted to the unique features of sodium MRI in tumor animal models, mainly in glioma, performed at 9.4 and 21.1 T. The ability of sodium MRI to monitor tumor response to therapy was evaluated. It is noteworthy that sodium MRI can detect glioma response to chemotherapy earlier than diffusion MRI. Especially attractive is the ability of sodium MRI to predict tumor therapeutic resistance before therapy. The non-invasive prediction of tumor chemo-resistance by sodium MRI presents a potential to individualize strategies for cancer treatment. Specifics of sodium MRI and technical aspects of imaging are also presented. Copyright © 2015 John Wiley & Sons, Ltd. [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]

Lung cancer is the leading cause of cancer-related deaths worldwide, and even today, the 5-year survival rate is still below 15 %. Lung adenocarcinoma is the most frequent subtype, and approximately 25 % of the cases harbor activating mutations in the KRAS gene. To date, there is no effective treatment for patients carrying KRAS mutations due, at least in part, to the challenge posed by direct targeting of the KRAS oncoprotein. During the last decade, scientists have developed genetically engineered mouse models that faithfully recapitulate the natural history of the human tumors. These models have been used as a preclinical platform to validate a number of relevant downstream effectors of KRAS signaling. Targets displaying synthetic lethality with the KRAS oncoprotein have also been validated in these models. Here, we review these studies and discuss their potential value in the clinical setting. We also provide an outlook as of how to improve the significance of target validation studies in preclinical platforms. [ABSTRACT FROM AUTHOR]

An area of rapid advancement in abdominal MRI is diffusion-weighted imaging (DWI). By measuring diffusion properties of water molecules, DWI is capable of non-invasively probing tissue properties and physiology at cellular and macromolecular level. The integration of DWI as part of abdominal MRI exam allows better lesion characterization and therefore more accurate initial diagnosis and treatment monitoring. One of the most technical challenging, but also most useful abdominal DWI applications is in liver and therefore requires special attention and careful optimization. In this article, the latest technical developments of DWI and its liver applications are reviewed with the explanations of the technical principles, recommendations of the imaging parameters, and examples of clinical applications. More advanced DWI techniques, including Intra-Voxel Incoherent Motion (IVIM) diffusion imaging, anomalous diffusion imaging, and Diffusion Kurtosis Imaging (DKI) are discussed. [ABSTRACT FROM AUTHOR]

Given the merit of high-resolution cross-sectional imaging, magnetic resonance imaging (MRI) has been utilized in many preclinical and clinical research fields. In addition to T2-weighted imaging for assessing anatomic changes by disease and therapeutic agents, diffusion-weighted imaging, dynamic contrast-enhanced MRI, and MR spectroscopy can provide disease- and drug-specific functional information in both in vivo and ex vivo status. Another advantage of MRI is its ability to bridge the preclinical and clinical experiments as it allows similar study methods and environments between animals and humans. Therefore, MRI can be used as a useful tool for drug development. Investigators have discovered a variety of MRI biomarkers that can quantitatively measure the biological alteration led by disease and treatment. In this chapter, a number of commonly used preclinical MRI biomarkers for drug development will be introduced and discussed, particularly being focused on their value for translational research.

Protein posttranslational modifications (PTMs) regulate intracellular signaling associated with development and progression of many diseases; thus, they are key to understanding pathological mechanisms and set up more tailored therapies. In addition, many posttranslationally modified proteins are released into biological fluids and can be used as new and more specific biomarkers. Based on this evidence, we analyzed the role of some PTMs in cancer and described the correlation between specific PTMs and T-cells activation/inhibition in cancer microenvironment. In the second part of this chapter, we analyzed the most commonly used approaches for qualitative and quantitative determination of PTMs. The comparison of three distinct but often complementary methodologies such as immunoblotting, mass spectrometry, and ELISA assays has allowed to highlight the pros and cons of each approach with a focus on their current application and their future developments to obtain more confident biomarkers and therapeutic targets useful for diagnosis, prognosis, and monitoring of the response to therapy.

Key Clinical Message: Our case highlights a series of bone marrow biopsies from a patient with primary myelofibrosis. Over time, this patient developed an unusual fatty appearance to his marrow, confirmed on multiple biopsies. This finding was supported by a quantitative fat MRI sequence that also shows a fatty appearance to the marrow. [ABSTRACT FROM AUTHOR]

Objectives: Conventional spin-echo (SE) DWI leads to a fundamental trade-off depending on the b value: high b value provides better lesion contrast-to-noise ratio (CNR) by sacrificing signal-to-noise ratio (SNR), image quality, and quantitative reliability. A stimulated-echo (STE) DWI acquisition is evaluated for high-CNR imaging of prostate cancer while maintaining SNR and reliable apparent diffusion coefficient (ADC) mapping., Methods: In this prospective, IRB-approved study, 27 patients with suspected prostate cancer (PCa) were scanned with three DWI sequences (SE b = 800 s/mm 2 , SE b = 1500 s/mm 2 , and STE b = 800 s/mm 2 ) after informed consent was obtained. ROIs were drawn on biopsy-confirmed cancer and non-cancerous tissue to perform quantitative SNR, CNR, and ADC measurements. Qualitative metrics (SNR, CNR, and overall image quality) were evaluated by three experienced radiologists. Metrics were compared pairwise between the three acquisitions using a t test (quantitative metrics) and Wilcoxon rank test (qualitative metrics)., Results: Quantitative measurements showed that STE DWI at b = 800 s/mm 2 has significantly better SNR compared to SE DWI at b = 1500 s/mm 2 (p < 0.0001) and comparable CNR to high-b value SE DWI at b = 1500 s/mm 2 (p < 0.05) in the peripheral zone. Qualitative assessment showed preference to STE b = 800 s/mm 2 in SNR and SE b = 1500 s/mm 2 in CNR. The overall image quality and lesion detectability among most readers showed no significant preference between STE b = 800 s/mm 2 and SE b = 1500 s/mm 2 . Further, STE DWI had similar ADC contrast between lesion and normal tissue as SE DWI at b = 800 s/mm 2 (p = 0.90)., Conclusion: STE DWI has the potential to provide high-SNR, high-CNR imaging of prostate cancer while also enabling reliable ADC mapping., Key Points: • Quantitative analysis showed that STE DWI at b = 800 s/mm 2 is able to achieve simultaneously high CNR, high SNR, and reliable ADC mapping, compared to SE b = 800 s/mm 2 and SE b = 1500 s/mm 2 . • Qualitative assessment by three readers showed that STE DWI at b = 800 s/mm 2 has significantly higher SNR than SE b = 1500 s/mm 2 . No preference between SE b = 1500 s/mm 2 and STE b = 800 s/mm 2 was determined in terms of CNR with no missed lesions were found in both acquisitions. • A single STE DWI acquisition at moderate b value (800-1000 s/mm 2 ) may provide sufficient image quality and quantitative reliability for prostate cancer imaging within a shorter scan time, in place of two DWI acquisitions (one with moderate b value and one with high b value).

Objective: To determine which outcome measures could detect early progression of disease in school-age children with mild cystic fibrosis (CF) lung disease over a two-year time interval utilizing chest computed tomography (CT) scores, quantitative CT air trapping (QAT), and spirometric measurements., Methods: Thirty-six school-age children with mild CF lung disease (median [interquartile range] age 12 [3.7] years; percent predicted forced expiratory volume in 1 second (ppFEV 1 ) 99 [12.5]) were evaluated by serial spirometer-controlled chest CT scans and spirometry at baseline, 3-month, 1- and 2-years., Results: No significant changes were noted at 3-month for any variable except for decreased ppFEV 1 . Mucus plugging score (MPS) and QAT A1 and A2 increased at 1- and 2-years. The bronchiectasis score (BS), and total score (TS) were increased at 2-year. All variables tested with the exception of bronchial wall thickness score, parenchymal score (PS), and ppFEV 1 , were consistent with longitudinal worsening of lung disease. Multivariate analysis revealed baseline PS, baseline TS, and 1-year changes in BS and air trapping score were predictive of 2-year changes in BS., Conclusions: MPS and QAT A1-A2 were the most sensitive indicators of progressive childhood CF lung disease. The 1-year change in the bronchiectasis score had the most positive predictive power for 2-year change in bronchiectasis., (© 2020 Wiley Periodicals, Inc.)

The aim of this study was to determine the ability of multiparametric MRI to identify the early effects of individual treatment, during combined chemo-radiotherapy on brain tumours. Eighty male rats bearing 9L gliosarcomas were randomized into four groups: untreated, anti-angiogenic therapy (SORA group), microbeam radiation therapy (MRT group) and both treatments (MRT+SORA group). Multiparametric MRI (tumour volume, diffusion-weighted MR imaging (ADC), blood volume fraction (BVf), microvessel index (VSI), vessel wall integrity (AUCP846) and tissue oxygen saturation (StO2)) was performed 1 day before and 2, 5 and 8 days after treatment initiation. Unpaired t-tests and one-way ANOVA were used for statistical analyses. Each MR parameter measured in our protocol was revealed to be sensitive to tumour changes induced by any of the therapies used (individually or combined). When compared with untreated tumours, SORA induced a decrease in BVf, VSI, StO2 and AUCP846, MRT generated an increase in ADC and AUCP846 and combined therapies yielded mixed effects: an increase in ADC and AUCP846 and a decrease in BVf, StO2 and AUCP846. MRT and MRT+SORA significantly slowed tumour growth. Despite these two groups presenting with similar tumour sizes, the information yielded from MR multiparameter assessment indicated that, when used concomitantly, each therapy induced distinguishable and appreciable physiological changes in the tumour. Our results suggest that multiparametric MRI can monitor the effects of individual treatments, used concomitantly, on brain tumours. Such monitoring would be useful for the detection of tumour resistance to drug/radiotherapy in patients undergoing concomitant therapies. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Personalized medicine is based on the concept that individuals differ from one another. Chronic obstructive pulmonary disease (COPD) is particularly in need of a personalized medicine strategy. However, while the COPD population is characterized by a marked degree of heterogeneity at the etiologic, mechanistic, physiologic, and clinical levels, efforts to cluster COPD patients into meaningful groups that can guide therapy have been limited. Three large observational studies--the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE), the Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS), and COPDGene--are underway and/or being analyzed. These studies have accumulated a uniquely rich set of clinical and biological data on relatively large cohorts of patients who have already influenced the way in which COPD is viewed. These studies have great potential to advance understanding of COPD so that the goal of personalized treatment can be pursued. [ABSTRACT FROM AUTHOR]