Primary Rectal Cancer: Repeatability of Global and Local-Regional MR Imaging Texture Features.

Purpose To assess the day-to-day repeatability of global and local-regional magnetic resonance (MR) imaging texture features derived from primary rectal cancer. Materials and Methods After ethical approval and patient informed consent were obtained, two pretreatment T2-weighted axial MR imaging studies performed prospectively with the same imaging unit on 2 consecutive days in 14 patients with rectal cancer (11 men [mean age, 61.7 years], three women [mean age, 70.0 years]) were analyzed to extract (a) global first-order statistical histogram and model-based fractal features reflecting the whole-tumor voxel intensity histogram distribution and repeating patterns, respectively, without spatial information and (b) local-regional second-order and high-order statistical texture features reflecting the intensity and spatial interrelationships between adjacent in-plane or multiplanar voxels or regions, respectively. Repeatability was assessed for 46 texture features, and mean difference, 95% limits of agreement, within-subject coefficient of variation (wCV), and repeatability coefficient (r) were recorded. Results Repeatability was better for global parameters than for most local-regional parameters. In particular, histogram mean, median, and entropy, fractal dimension mean and standard deviation, and second-order entropy, homogeneity, difference entropy, and inverse difference moment demonstrated good repeatability, with narrow limits of agreement and wCVs of 10% or lower. Repeatability was poorest for the following high-order gray-level run-length (GLRL) gray-level zone size matrix (GLZSM) and neighborhood gray-tone difference matrix (NGTDM) parameters: GLRL intensity variability, GLZSM short-zone emphasis, GLZSM intensity nonuniformity, GLZSM intensity variability, GLZSM size zone variability, and NGTDM complexity, demonstrating wider agreement limits and wCVs of 50% or greater. Conclusion MR imaging repeatability is better for global texture parameters than for local-regional texture parameters, indicating that global texture parameters should be sufficiently robust for clinical practice. Online supplemental material is available for this article.

The precision of textural analysis in (18)F-FDG-PET scans of oesophageal cancer.

OBJECTIVES: Measuring tumour heterogeneity by textural analysis in (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) provides predictive and prognostic information but technical aspects of image processing can influence parameter measurements. We therefore tested effects of image smoothing, segmentation and quantisation on the precision of heterogeneity measurements. METHODS: Sixty-four (18)F-FDG PET/CT images of oesophageal cancer were processed using different Gaussian smoothing levels (2.0, 2.5, 3.0, 3.5, 4.0 mm), maximum standardised uptake value (SUVmax) segmentation thresholds (45%, 50%, 55%, 60%) and quantisation (8, 16, 32, 64, 128 bin widths). Heterogeneity parameters included grey-level co-occurrence matrix (GLCM), grey-level run length matrix (GLRL), neighbourhood grey-tone difference matrix (NGTDM), grey-level size zone matrix (GLSZM) and fractal analysis methods. The concordance correlation coefficient (CCC) for the three processing variables was calculated for each heterogeneity parameter. RESULTS: Most parameters showed poor agreement between different bin widths (CCC median 0.08, range 0.004-0.99). Segmentation and smoothing showed smaller effects on precision (segmentation: CCC median 0.82, range 0.33-0.97; smoothing: CCC median 0.99, range 0.58-0.99). CONCLUSIONS: Smoothing and segmentation have only a small effect on the precision of heterogeneity measurements in (18)F-FDG PET data. However, quantisation often has larger effects, highlighting a need for further evaluation and standardisation of parameters for multicentre studies. KEY POINTS: • Heterogeneity measurement precision in (18) F-FDG PET is influenced by image processing methods. • Quantisation shows large effects on precision of heterogeneity parameters in (18) F-FDG PET/CT. • Smoothing and segmentation show comparatively smaller effects on precision of heterogeneity parameters.

Imaging of site specific bone turnover in osteoporosis using positron emission tomography.

The functional imaging technique of dynamic fluorine-18 labeled sodium fluoride positron emission tomography ((18)F-NaF PET) allows the quantitative assessment of regional bone formation by measuring the plasma clearance of fluoride to bone at any site in the skeleton. (18)F-NaF PET provides a novel and noninvasive method of studying site-specific bone formation at the hip and spine, as well as areas of pure cortical or trabecular bone. The technique complements conventional measurements of bone turnover using biochemical markers and bone biopsy as a tool to investigate new treatments for osteoporosis, and holds promise of a future role as an early biomarker of treatment efficacy in clinical trials. This article reviews methods of acquiring and analyzing (18)F-NaF PET scan data, and outlines a simplified approach that uses 5-minute static PET scan images combined with venous blood samples to estimate (18)F-NaF plasma clearance at multiple sites in the skeleton with a single injection of tracer.

Quantifying tumour heterogeneity in 18F-FDG PET/CT imaging by texture analysis.

(18)F-Fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) is now routinely used in oncological imaging for diagnosis and staging and increasingly to determine early response to treatment, often employing semiquantitative measures of lesion activity such as the standardized uptake value (SUV). However, the ability to predict the behaviour of a tumour in terms of future therapy response or prognosis using SUVs from a baseline scan prior to treatment is limited. It is recognized that medical images contain more useful information than may be perceived with the naked eye, leading to the field of "radiomics" whereby additional features can be extracted by computational postprocessing techniques. In recent years, evidence has slowly accumulated showing that parameters obtained by texture analysis of radiological images, reflecting the underlying spatial variation and heterogeneity of voxel intensities within a tumour, may yield additional predictive and prognostic information. It is hoped that measurement of these textural features may allow better tissue characterization as well as better stratification of treatment in clinical trials, or individualization of future cancer treatment in the clinic, than is possible with current imaging biomarkers. In this review we focus on the literature describing the emerging methods of texture analysis in (18)FDG PET/CT, as well as other imaging modalities, and how the measurement of spatial variation of voxel grey-scale intensity within an image may provide additional predictive and prognostic information, and postulate the underlying biological mechanisms.

(18)F-fluoride positron emission tomography measurements of regional bone formation in hemodialysis patients with suspected adynamic bone disease.

(18)F-fluoride positron emission tomography ((18)F-PET) allows the assessment of regional bone formation and could have a role in the diagnosis of adynamic bone disease (ABD) in patients with chronic kidney disease (CKD). The purpose of this study was to examine bone formation at multiple sites of the skeleton in hemodialysis patients (CKD5D) and assess the correlation with bone biopsy. Seven CKD5D patients with suspected ABD and 12 osteoporotic postmenopausal women underwent an (18)F-PET scan, and bone plasma clearance, K i, was measured at ten skeletal regions of interest (ROI). Fifteen subjects had a transiliac bone biopsy following double tetracycline labeling. Two CKD5D patients had ABD confirmed by biopsy. There was significant heterogeneity in K i between skeletal sites, ranging from 0.008 at the forearm to 0.028 mL/min/mL at the spine in the CKD5D group. There were no significant differences in K i between the two study groups or between the two subjects with ABD and the other CKD5D subjects at any skeletal ROI. Five biopsies from the CKD5D patients had single tetracycline labels only, including the two with ABD. Using an imputed value of 0.3 µm/day for mineral apposition rate (MAR) for biopsies with single labels, no significant correlations were observed between lumbar spine K i corrected for BMAD (K i/BMAD) and bone formation rate (BFR/BS), or MAR. When biopsies with single labels were excluded, a significant correlation was observed between K i/BMAD and MAR (r = 0.81, p = 0.008) but not BFR/BS. Further studies are required to establish the sensitivity of (18)F-PET as a diagnostic tool for identifying CKD patients with ABD.

Estimation of regional bone metabolism from whole-body 18F-fluoride PET static images.

PURPOSE: We evaluate a new quantitative method of acquiring and analysing (18)F positron emission tomography (PET) studies that enables regional bone plasma clearance (K ( i )) to be estimated from static scans acquired at multiple sites in the skeleton following a single injection of tracer. METHODS: Dynamic lumbar spine (18)F PET data from two clinical trials were used to simulate a series of static scans acquired 30-60 min after injection. Venous blood samples were taken at 30, 40, 50 and 60 min and K ( i ) evaluated by Patlak analysis and the static scan method. The data were used to evaluate the precision errors of the Patlak and static scan methods expressed as the percentage coefficient of variation (%CV) and compare their response to 6 months of treatment with the bone anabolic agent teriparatide. RESULTS: Static scan K ( i ) measurements 30-60 min after injection were highly correlated with the Patlak results (r > 0.99). The %CV for the static scan method was 17.5% 30 min after injection, decreasing to 14.5% at 60 min, compared with 13.0% for Patlak analysis. Response to teriparatide treatment was +25.2% for the static scan method compared with +24.3% for Patlak analysis. The mean ratio (SD) of the static scan and Patlak K ( i ) results was 1.006 (0.015) at 30 min after injection decreasing to 0.965 (0.015) at 60 min. CONCLUSION: (18)F-Fluoride bone plasma clearance can be estimated from a static scan and venous blood samples acquired 30-60 min after injection. The method enables K ( i ) to be estimated at multiple skeletal sites with a single injection of tracer.

The assessment of regional skeletal metabolism: studies of osteoporosis treatments using quantitative radionuclide imaging.

Studies of bone remodeling using bone biopsy and biochemical markers of bone turnover play an important role in research studies to investigate the effect of new osteoporosis treatments on bone quality. Quantitative radionuclide imaging using either positron emission tomography with fluorine-18 sodium fluoride or gamma camera studies with technetium-99m methylene diphosphonate provides a novel tool for studying bone metabolism that complements conventional methods, such as bone turnover markers (BTMs). Unlike BTMs, which measure the integrated response to treatment across the whole skeleton, radionuclide imaging can distinguish the changes occurring at sites of particular clinical interest, such as the spine or proximal femur. Radionuclide imaging can be used to measure either bone uptake or (if done in conjunction with blood sampling) bone plasma clearance. Although the latter is more complicated to perform, unlike bone uptake, it provides a measurement that is specific to the bone metabolic activity at the measurement site. Treatment with risedronate was found to cause a decrease in bone plasma clearance, whereas treatment with the bone anabolic agent teriparatide caused an increase. Studies of teriparatide are of particular interest because the treatment has different effects at different sites in the skeleton, with a substantially greater response in the flat bone of the skull and cortical bone in the femur compared with the lumbar spine. Future studies should include investigations of osteonecrosis of the jaw and atypical fractures of the femur to examine the associated regional changes in bone metabolism and to throw light on the underlying pathologies.

A Short Dynamic Scan Method of Measuring Bone Metabolic Flux Using [18F]NaF PET.

[18F]NaF PET measurements of bone metabolic flux (Ki) are conventionally obtained with 60-min dynamic scans analysed using the Hawkins model. However, long scan times make this method expensive and uncomfortable for subjects. Therefore, we evaluated and compared measurements of Ki with shorter scan times analysed with fixed values of the Hawkins model rate constants. The scans were acquired in a trial in 30 postmenopausal women, half treated with teriparatide (TPT) and half untreated. Sixty-minute PET-CT scans of both hips were acquired at baseline and week 12 after injection with 180 MBq [18F]NaF. Scans were analysed using the Hawkins model by fitting bone time-activity curves at seven volumes of interest (VOIs) with a semi-population arterial input function. The model was re-run with fixed rate-constants for dynamic scan times from 0-12 min increasing in 4-min steps up to 0-60 min. Using the Hawkins model with fixed rate-constants, Ki measurements with statistical power equivalent or superior to conventionally analysed 60-min dynamic scans were obtained with scan times as short as 12 min.

Artificial intelligence in medical imaging: A radiomic guide to precision phenotyping of cardiovascular disease.

ABSTRACT: Rapid technological advances in non-invasive imaging, coupled with the availability of large data sets and the expansion of computational models and power, have revolutionized the role of imaging in medicine. Non-invasive imaging is the pillar of modern cardiovascular diagnostics, with modalities such as cardiac computed tomography (CT) now recognized as first-line options for cardiovascular risk stratification and the assessment of stable or even unstable patients. To date, cardiovascular imaging has lagged behind other fields, such as oncology, in the clinical translational of artificial intelligence (AI)-based approaches. We hereby review the current status of AI in non-invasive cardiovascular imaging, using cardiac CT as a running example of how novel machine learning (ML)-based radiomic approaches can improve clinical care. The integration of ML, deep learning, and radiomic methods has revealed direct links between tissue imaging phenotyping and tissue biology, with important clinical implications. More specifically, we discuss the current evidence, strengths, limitations, and future directions for AI in cardiac imaging and CT, as well as lessons that can be learned from other areas. Finally, we propose a scientific framework in order to ensure the clinical and scientific validity of future studies in this novel, yet highly promising field. Still in its infancy, AI-based cardiovascular imaging has a lot to offer to both the patients and their doctors as it catalyzes the transition towards a more precise phenotyping of cardiovascular disease.

Teriparatide Promotes Bone Healing in Medication-Related Osteonecrosis of the Jaw: A Placebo-Controlled, Randomized Trial.

PURPOSE: Medication-related osteonecrosis of the jaw (MRONJ) is an infrequent but morbid and potentially serious condition associated with antiresorptive and antiangiogenic therapies. Although MRONJ can be prevented by optimizing oral health, management of established cases is supportive and remains challenging. Teriparatide, an osteoanabolic agent that improves bone healing in preclinical studies and in chronic periodontitis, represents a potential treatment option. PATIENTS AND METHODS: In a double-blind, randomized, controlled trial, 34 participants with established MRONJ, with a total of 47 distinct MRONJ lesions, were allocated to either 8 weeks of subcutaneous teriparatide (20 µg/day) or placebo injections, in addition to calcium and vitamin D supplementation and standard clinical care. Participants were observed for 12 months, with primary outcomes that included the clinical and radiologic resolution of MRONJ lesions. Secondary outcomes included osteoblastic responses as measured biochemically and radiologically and changes in quality of life. RESULTS: Teriparatide was associated with a greater rate of resolution of MRONJ lesions (odds ratio [OR], 0.15 v 0.40; P = .013), and 45.4% of lesions resolved by 52 weeks compared with 33.3% in the placebo group. Teriparatide was also associated with reduced bony defects at week 52 (OR, 8.1; P = .017). The incidence of adverse events was balanced between groups, including nausea, anorexia, and musculoskeletal pain, most of mild severity. CONCLUSION: Teriparatide improves the rate of resolution of MRONJ lesions and represents an efficacious and safe treatment for it.

Radiomics in esophageal and gastric cancer.

Esophageal, esophago-gastric, and gastric cancers are major causes of cancer morbidity and cancer death. For patients with potentially resectable disease, multi-modality treatment is recommended as it provides the best chance of survival. However, quality of life may be adversely affected by therapy, and with a wide variation in outcome despite multi-modality therapy, there is a clear need to improve patient stratification. Radiomic approaches provide an opportunity to improve tumor phenotyping. In this review we assess the evidence to date and discuss how these approaches could improve outcome in esophageal, esophago-gastric, and gastric cancer.

The influence of CT and dual-energy X-ray absorptiometry (DXA) bone density on quantitative [18F] sodium fluoride PET.

BACKGROUND: [18F] sodium fluoride PET/CT provides quantitative measures of bone metabolic activity expressed by the parameters standardised uptake value (SUV) and bone plasma clearance (K i) that correlate with measurements of bone formation rate obtained by bone biopsy with double tetracycline labelling. Both SUV and K i relate to the tracer uptake in each millilitre of tissue. In general, the bone region of interest (ROI) includes both mineralised bone {generally with a high concentration of [18F]NaF} and bone marrow (with a much lower concentration), suggesting that correcting SUV and K i for volumetric bone mineral density (vBMD) and measuring them with respect to the tracer uptake in each gram of bone mineral might improve the correlation with the findings of bone biopsy. As a first test of this hypothesis, we looked for positive correlations between SUV and K i values with CT and DXA bone mineral density (BMD) parameters measured in the same ROI. METHODS: A retrospective reanalysis was performed of 63 lumbar spine [18F]NaF PET/CT scans acquired in four earlier studies. The quantitative PET parameters SUV and K i were measured in L1-L4 and Hounsfield units (HU) measured on the CT scans in the same ROI. Spine BMD data was also obtained from DXA scans in the form of areal BMD and used to derive the bone mineral apparent density (BMAD, an estimate of vBMD). Scatter plots were drawn of SUV and K i against HU, BMAD and areal BMD and the Spearman rank correlation coefficients derived for each plot. RESULTS: All correlations were positive and statistically significant. Correlations were highest for HU (SUV: RS =0.513, P<0.0001; K i: RS =0.429, P=0.0005) and lowest for areal BMD (SUV: RS =0.353, P=0.005; K i: RS =0.274, P=0.03). CONCLUSIONS: The results demonstrate significant positive correlations between SUV and K i and vBMD measurements in the form of HU from CT or BMAD and areal BMD from DXA. These findings justify further exploration of the relationship between SUV and K i [18F]NaF PET/CT measurements and CT or DXA measurements of vBMD to examine whether normalization for bone density might improve their correlation with bone metabolic activity as measured by bone biopsy.

Does Measurement of First-Order and Heterogeneity Parameters Improve Response Assessment of Bone Metastases in Breast Cancer Compared to SUVmax in [18F]fluoride and [18F]FDG PET?

PURPOSE: To establish whether first-order statistical features from [18F]fluoride and 2-deoxy-2-[18F] fluoro-D-glucose ([18F]FDG) positron emission tomography/x-ray computed tomography (PET/CT) demonstrate incremental value in skeletal metastasis response assessment compared with maximum standardised uptake value (SUVmax). PROCEDURES: Sixteen patients starting endocrine treatment for de novo or progressive breast cancer bone metastases were prospectively recruited to undergo [18F]fluoride and [18F]FDG PET/CT scans before and 8 weeks after treatment. Percentage changes in SUV parameters, metabolic tumour volume (MTV), total lesion metabolism (TLM), standard deviation (SD), entropy, uniformity and absolute changes in kurtosis and skewness, from the same ≤ 5 index lesions, were measured. Clinical response to 24 weeks, assessed by two experienced oncologists blinded to PET/CT imaging findings, was used as a reference standard and associations were made between parameters and progression free and overall survival. RESULTS: [18F]fluoride PET/CT: In four patients (20 lesions) with progressive disease (PD), TLM and kurtosis predicted PD better than SUVmax on a patient basis (4, 4 and 3 out of 4, respectively) and TLM, entropy, uniformity and skewness on a lesion basis (18, 16, 16, 18 and 15 out of 20, respectively). Kurtosis was independently associated with PFS (p = 0.033) and OS (p = 0.008) on Kaplan-Meier analysis. [18F]FDG PET: No parameter provided incremental value over SUVmax in predicting PD or non-PD. TLM was significantly associated with OS (p = 0.041) and skewness with PFS (p = 0.005). Interlesional heterogeneity of response was seen in 11/16 and 8/16 patients on [18F]fluoride and [18F]FDG PET/CT, respectively. CONCLUSION: With [18F]fluoride PET/CT, some first-order features, including those that take into account lesion volume but also some heterogeneity parameters, provide incremental value over SUVmax in predicting clinical response and survival in breast cancer patients with bone metastases treated with endocrine therapy. With [18F]FDG PET/CT, no first-order parameters were more accurate than SUVmax although TLM and skewness were associated with OS and PFS, respectively. Intra-patient heterogeneity of response occurs commonly between metastases with both tracers and most parameters.

Is Response Assessment of Breast Cancer Bone Metastases Better with Measurement of 18F-Fluoride Metabolic Flux Than with Measurement of 18F-Fluoride PET/CT SUV?

Our purpose was to establish whether noninvasive measurement of changes in 18F-fluoride metabolic flux to bone mineral (Ki) by PET/CT can provide incremental value in response assessment of bone metastases in breast cancer compared with SUVmax and SUVmeanMethods: Twelve breast cancer patients starting endocrine treatment for de novo or progressive bone metastases were included. Static 18F-fluoride PET/CT scans were acquired 60 min after injection, before and 8 wk after commencing treatment. Venous blood samples were taken at 55 and 85 min after injection to measure plasma 18F-fluoride activity concentrations, and Ki in individual bone metastases was calculated using a previously validated method. Percentage changes in Ki, SUVmax, and SUVmean were calculated from the same index lesions (≤5 lesions) from each patient. Clinical response up to 24 wk, assessed in consensus by 2 experienced oncologists masked to PET imaging findings, was used as a reference standard. Results: Of the 4 patients with clinically progressive disease (PD), mean Ki significantly increased (>25%) in all, SUVmax in 3, and SUVmean in 2. Of the 8 non-PD patients, Ki decreased or remained stable in 7, SUVmax in 5, and SUVmean in 6. A significant mean percentage increase from baseline for Ki, compared with SUVmax and SUVmean, occurred in the 4 patients with PD (89.7% vs. 41.8% and 43.5%, respectively; P < 0.001). Conclusion: After 8 wk of endocrine treatment for bone-predominant metastatic breast cancer, Ki more reliably differentiated PD from non-PD than did SUVmax and SUVmean, probably because measurement of SUV underestimates fluoride clearance by not considering changes in input function.

Challenges and Promises of PET Radiomics.

PURPOSE: Radiomics describes the extraction of multiple, otherwise invisible, features from medical images that, with bioinformatic approaches, can be used to provide additional information that can predict underlying tumor biology and behavior. METHODS AND MATERIALS: Radiomic signatures can be used alone or with other patient-specific data to improve tumor phenotyping, treatment response prediction, and prognosis, noninvasively. The data describing 18F-fluorodeoxyglucose positron emission tomography radiomics, often using texture or heterogeneity parameters, are increasing rapidly. RESULTS: In relation to radiation therapy practice, early data have reported the use of radiomic approaches to better define tumor volumes and predict radiation toxicity and treatment response. CONCLUSIONS: Although at an early stage of development, with many technical challenges remaining and a need for standardization, promise nevertheless exists that PET radiomics will contribute to personalized medicine, especially with the availability of increased computing power and the development of machine-learning approaches for imaging.

Site specific measurements of bone formation using [18F] sodium fluoride PET/CT.

Dynamic positron emission tomography (PET) imaging with fluorine-18 labelled sodium fluoride ([18F]NaF) allows the quantitative assessment of regional bone formation by measuring the plasma clearance of fluoride to bone at any site in the skeleton. Today, hybrid PET and computed tomography (CT) dual-modality systems (PET/CT) are widely available, and [18F]NaF PET/CT offers a convenient non-invasive method of studying bone formation at the important osteoporotic fracture sites at the hip and spine, as well as sites of pure cortical or trabecular bone. The technique complements conventional measurements of bone turnover using biochemical markers or bone biopsy as a tool to investigate new therapies for osteoporosis, and has a potential role as an early biomarker of treatment efficacy in clinical trials. This article reviews methods of acquiring and analyzing dynamic [18F]NaF PET/CT scan data, and outlines a simplified approach combining venous blood sampling with a series of short (3- to 5-minute) static PET/CT scans acquired at different bed positions to estimate [18F]NaF plasma clearance at multiple sites in the skeleton with just a single injection of tracer.

Application of automated medial temporal lobe atrophy scale to Alzheimer disease.

OBJECTIVE: To compare an automated intensity-based measure of medial temporal atrophy in Alzheimer disease (AD) with existing volumetric and visually based methods. DESIGN: Longitudinal study comparing a medial temporal atrophy measure with 2 criterion standards: (1) total hippocampal (HC) volume adjusted for total intracranial volume and (2) standard visual rating scale of medial temporal atrophy. SETTING: Cognitive disorders specialist clinic. PARTICIPANTS: Forty-seven patients with AD and 26 age- and sex-matched controls. INTERVENTION: Subjects were scanned using volumetric T1-weighted magnetic resonance imaging at baseline and 1 year later. MAIN OUTCOME MEASURE: Automated Medial Temporal Lobe Atrophy Scale (ATLAS) score, derived from dividing mean intensity of a standardized perihippocampal volume by that of a standardized pontine volume. RESULTS: Patients with AD had significantly reduced ATLAS scores and HC volumes and increased visual rating scores at baseline and repeat scanning. Rates of HC atrophy and decline in the ATLAS score were significantly higher in patients with AD compared with controls. The ATLAS scores were significantly correlated with HC volumes and visual rating scores. With specificity set at 85%, the sensitivities of HC volume and visual rating scale score were similar (84% and 86%, respectively), whereas ATLAS score had a lower sensitivity (73%). At repeat scanning, all 3 measures had similar sensitivities (86%-87%). Rate of decline in the ATLAS score required a similar sample size to HC atrophy rate to provide statistical power to clinical trials, but being automated, it is less labor intensive. CONCLUSIONS: Like the visual rating scale, ATLAS is a simple medial temporal atrophy measure, which has the additional advantage of being able to track AD progression on serial imaging.

Magnetic Resonance Imaging (MRI) of Intratumoral Voxel Heterogeneity as a Potential Response Biomarker: Assessment in a HER2+ Esophageal Adenocarcinoma Xenograft Following Trastuzumab and/or Cisplatin Therapy.

We evaluated magnetic resonance imaging (MRI) voxel heterogeneity following trastuzumab and/or cisplatin in a HER2+ esophageal xenograft (OE19) as a potential response biomarker. OE19 xenografts treated with saline (controls), monotherapy, or combined cisplatin and trastuzumab underwent 9.4-T MRI. Tumor MRI parametric maps of T1 relaxation time (pre/post contrast), T2 relaxation time, T2* relaxation rate (R2*), and apparent diffusion coefficient obtained before (TIME0), after 24hours (TIME1), and after 2weeks of treatment (TIME2) were analyzed. Voxel histogram and fractal parameters (from the whole tumor, rim and center, and as a ratio of rim-to-center) were derived. Tumors were stained for immunohistochemical markers of hypoxia (CA-IX), angiogenesis (CD34), and proliferation (Ki-67). Combination therapy reduced xenograft growth rate (relative change, ∆ +0.58±0.43 versus controls, ∆ +4.1±1.0; P=0.008). More spatially homogeneous voxel distribution between the rim to center was noted after treatment for combination therapy versus controls, respectively, for contrast-enhanced T1 relaxation time (90th percentile: ratio 1.00 versus 0.88, P=0.009), T2 relaxation time (mean: 1.00 versus 0.92, P=0.006; median: 0.98 versus 0.91, P=0.006; 75th percentile: 1.02 versus 0.94, P=0.007), and R2* (10th percentile: 0.99 versus 1.26, P=0.003). We found that combination and trastuzumab monotherapy reduced MRI spatial heterogeneity and growth rate compared to the control or cisplatin groups, the former providing adjunctive tumor response information.

The effect of post-injection 18F-FDG PET scanning time on texture analysis of peripheral nerve sheath tumours in neurofibromatosis-1.

BACKGROUND: Texture features are being increasingly evaluated in 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) as adjunctive imaging biomarkers in a number of different cancers. Whilst studies have reported repeatability between scans, there have been no studies that have specifically investigated the effect that the time of acquisition post-injection of 18F-FDG has on texture features. The aim of this study was to investigate if texture features change between scans performed at different time points post-injection. RESULTS: Fifty-four patients (30 male, 24 female, mean age 35.1 years) with neurofibromatosis-1 and suspected malignant transformation of a neurofibroma underwent 18F-FDG PET/computed tomography (CT) scans at 101.5 ± 15.0 and 251.7 ± 18.4 min post-injection of 350 MBq 18F-FDG to a standard clinical protocol. Following tumour segmentation on both early and late scans, first- (n = 37), second- (n = 25) and high-order (n = 31) statistical features, as well as fractal texture features (n = 6), were calculated and a comparison was made between the early and late scans for each feature. Of the 54 tumours, 30 were benign and 24 malignant on histological analysis or on clinical follow-up for at least 5 years. Overall, 25/37 first-order, 9/25 second-order, 13/31 high-order and 3/6 fractal features changed significantly (p < 0.05) between early and late scans. The corresponding proportions for the 30 benign tumours alone were 22/37, 7/25, 8/31 and 2/6 and for the 24 malignant tumours, 11/37, 6/25, 8/31 and 0/6, respectively. CONCLUSIONS: Several texture features change with time post-injection of 18F-FDG. Thus, when comparing texture features in intra- and inter-patient studies, it is essential that scans are obtained at a consistent time post-injection of 18F-FDG.

Imaging body composition in cancer patients: visceral obesity, sarcopenia and sarcopenic obesity may impact on clinical outcome.

UNLABELLED: In recent years, there has been increasing interest in the influence of body composition on oncological patient outcomes. Visceral obesity, sarcopenia and sarcopenic obesity have been identified as adverse factors in cancer patients. Imaging quantification of body composition such as lean muscle mass and fat distribution is a potentially valuable tool. This review describes the following imaging techniques that may be used to assess body composition: dual-energy X-ray absorptiometry (DXA), computed tomography (CT) and magnetic resonance imaging (MRI). CT and MRI are acquired as part of oncological patient care, thus providing an opportunity to integrate body composition assessment into the standard clinical pathway and allowing supportive care to be commenced as appropriate to improve outcome. MAIN MESSAGES: • Sarcopenia, sarcopenic obesity and visceral obesity are adverse prognostic factors in cancer patients. • CT and MRI are the current gold standard in body composition evaluation. • Body composition may affect chemotherapy tolerance and toxicities.