Medical imaging and nuclear medicine: a Lancet Oncology Commission.

The diagnosis and treatment of patients with cancer requires access to imaging to ensure accurate management decisions and optimal outcomes. Our global assessment of imaging and nuclear medicine resources identified substantial shortages in equipment and workforce, particularly in low-income and middle-income countries (LMICs). A microsimulation model of 11 cancers showed that the scale-up of imaging would avert 3·2% (2·46 million) of all 76·0 million deaths caused by the modelled cancers worldwide between 2020 and 2030, saving 54·92 million life-years. A comprehensive scale-up of imaging, treatment, and care quality would avert 9·55 million (12·5%) of all cancer deaths caused by the modelled cancers worldwide, saving 232·30 million life-years. Scale-up of imaging would cost US$6·84 billion in 2020-30 but yield lifetime productivity gains of $1·23 trillion worldwide, a net return of $179·19 per $1 invested. Combining the scale-up of imaging, treatment, and quality of care would provide a net benefit of $2·66 trillion and a net return of $12·43 per $1 invested. With the use of a conservative approach regarding human capital, the scale-up of imaging alone would provide a net benefit of $209·46 billion and net return of $31·61 per $1 invested. With comprehensive scale-up, the worldwide net benefit using the human capital approach is $340·42 billion and the return per dollar invested is $2·46. These improved health and economic outcomes hold true across all geographical regions. We propose actions and investments that would enhance access to imaging equipment, workforce capacity, digital technology, radiopharmaceuticals, and research and training programmes in LMICs, to produce massive health and economic benefits and reduce the burden of cancer globally.

Global Challenges for Cancer Imaging.

Imaging plays many essential roles in nearly all aspects of high-quality cancer care. However, challenges to the delivery of optimal cancer imaging in both developing and advanced countries are manifold. Developing countries typically face dramatic shortages of both imaging equipment and general radiologists, and efforts to improve cancer imaging in these countries are often complicated by poor infrastructure, cultural barriers, and other obstacles. In advanced countries, on the other hand, although imaging equipment and general radiologists are typically accessible, the complexity of oncologic imaging and the need for subspecialists in the field are largely unrecognized; as a result, training opportunities are lacking, and there is a shortage of radiologists with the necessary subspecialty expertise to provide optimal cancer care and participate in advanced clinical research. This article is intended to raise awareness of these challenges and catalyze further efforts to address them. Some promising strategies and ongoing efforts are reviewed, and some specific actions are proposed.

Assessment of Cervical Cancer with a Parameter-Free Intravoxel Incoherent Motion Imaging Algorithm.

OBJECTIVE: To evaluate the feasibility of a parameter-free intravoxel incoherent motion (IVIM) approach in cervical cancer, to assess the optimal b-value threshold, and to preliminarily examine differences in the derived perfusion and diffusion parameters for different histological cancer types. MATERIALS AND METHODS: After Institutional Review Board approval, 19 female patients (mean age, 54 years; age range, 37-78 years) gave consent and were enrolled in this prospective magnetic resonance imaging study. Clinical staging and biopsy results were obtained. Echo-planar diffusion weighted sequences at 13 b-values were acquired at 3 tesla field strength. Single-sliced region-of-interest IVIM analysis with adaptive b-value thresholds was applied to each tumor, yielding the optimal fit and the optimal parameters for pseudodiffusion (D*), perfusion fraction (Fp) and diffusion coefficient (D). Monoexponential apparent diffusion coefficient (ADC) was calculated for comparison with D. RESULTS: Biopsy revealed squamous cell carcinoma in 10 patients and adenocarcinoma in 9. The b-value threshold (median [interquartile range]) depended on the histological type and was 35 (22.5-50) s/mm2 in squamous cell carcinoma and 150 (100-150) s/mm2 in adenocarcinoma (p < 0.05). Comparing squamous cell vs. adenocarcinoma, D* (45.1 [25.1-60.4] × 10-3 mm2/s vs. 12.4 [10.5-21.2] × 10-3 mm2/s) and Fp (7.5% [7.0-9.0%] vs. 9.9% [9.0-11.4%]) differed significantly between the subtypes (p < 0.02), whereas D did not (0.89 [0.75-0.94] × 10-3 mm2/s vs. 0.90 [0.82-0.97] × 10-3 mm2/s, p = 0.27). The residuals did not differ (0.74 [0.60-0.92] vs. 0.94 [0.67-1.01], p = 0.32). The ADC systematically underestimated the magnitude of diffusion restriction compared to D (p < 0.001). CONCLUSION: The parameter-free IVIM approach is feasible in cervical cancer. The b-value threshold and perfusion-related parameters depend on the tumor histology type.

Intravoxel incoherent motion MRI assessment of chemoradiation-induced pelvic bone marrow changes in cervical cancer and correlation with hematological toxicity.

PURPOSE: To investigate bone marrow changes after chemoradiation (CRT) using intravoxel incoherent motion magnetic resonance imaging (IVIM-MRI) and correlate imaging changes with hematological toxicity (HT) in patients with locally advanced cervical cancer. MATERIALS AND METHODS: Thirty-nine patients with newly diagnosed cervical cancer were prospectively recruited for two sequential 3.0T IVIM-MRI studies: before treatment (MRI-1) and 3-4 weeks after standardized CRT (MRI-2). The irradiated pelvic bone marrow was outlined as the regions of interest to derive the true diffusion coefficient (D) and perfusion fraction (f) based on a biexponential model. The apparent coefficient diffusion (ADC) was derived using the monoexponential model. Changes in these parameters between MRI-1 and MRI-2 were calculated as ΔD, Δf, and ΔADC. HT was defined accordingly to NCI-CTCAE (v. 4.03) of grade 3 and above. Statistical analysis was performed using Mann-Whitney U-test. RESULTS: The median age of patients was 54 years old (range 27-83 years old); 14 patients suffered from HT. Early bone marrow changes (3-4 weeks) of ΔD showed a significant difference between HT and non-HT groups (6.4 ± 19.7% vs. -6.4 ± 19.4%, respectively, P = 0.041). However, no significant changes were noted in Δf (3.7 ± 13.3% vs. 1.5 ± 12.5% respectively, P = 0. 592) and ΔADC (5.5 ± 26.3% vs. -3.3 ± 27.0% respectively, P = 0.303) between the HT and non-HT groups. Δf increased insignificantly for both groups. CONCLUSION: ΔD was the only significant parameter to differentiate early cellular environment changes in bone marrow after CRT, suggestive that ΔD was more sensitive than Δf and ΔADC to reflect the underlying microenvironment injury. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1491-1498.

Evidence-Based Surveillance Imaging Schedule After Liver Transplantation for Hepatocellular Carcinoma Recurrence.

BACKGROUND: There is presently no evidence-based recommendation for surveillance of recurrent hepatocellular carcinoma after liver transplantation (LT). We aim to evaluate and develop evidence-based alternate surveillance imaging schedules for post-LT hepatocellular carcinoma patients. METHODS: Imaging and pathologic reports for consecutive post-LT patients followed up by regular surveillance imaging from a single institution's prospective database were evaluated with institutional review board approval. Outcome variable was time to diagnosis of first recurrence post-LT by surveillance imaging. Recurrence-free survival times from alternative surveillance schedules were compared with the existing schedule (every 3 months) using a parametric frailty model. Expected delay (EpD) in diagnosis compared to the existing schedule was also computed for the alternate surveillance schedules. A P value less than 0.05 was considered to indicate a significant difference. RESULTS: One hundred twenty-five patients (108 men; 59.4 ± 16.6 years) underwent 1953 computed tomography and 255 magnetic resonance imaging scans. Recurrence-free survival time was not significantly different in the first 5 years after LT when the imaging interval was extended from current every 3 months to every 6 months (P = 0.786, EpD = 55 days). This alternative schedule incurred 10 (50.0%) fewer surveillance scans than the 20 in the original schedule, and a corresponding reduction in radiation dose (if involved) and cost during the 5-year follow-up period. CONCLUSIONS: In conclusion, modeled alternative surveillance schedules have the potential to reduce the frequency of scans without compromising surveillance benefits.

Midtreatment ¹8F-FDG PET/CT Scan for Early Response Assessment of SMILE Therapy in Natural Killer/T-Cell Lymphoma: A Prospective Study from a Single Center.

UNLABELLED: In a prospective study of newly diagnosed or relapsed histologically proven extranodal natural killer/T-cell lymphoma (ENKTL) patients, we aimed to determine the accuracy of midtreatment (18)F-FDG PET for response assessment using both visual and quantitative analyses. METHODS: Twenty-four patients (12 men, 12 women; median age, 50 y; age range, 16-83 y) were referred for pre-, mid- (after 2-3 cycles of SMILE [prednisolone, methotrexate, ifosfamide, L-asparaginase, etoposide] chemotherapy), and end-treatment PET/CT scans (n = 24, 24, and 17, respectively) using a standardized protocol. Sixty-five PET/CT scans were analyzed visually using the Deauville 5-point score (DS), and the lesion with the highest maximum standardized uptake value (SUV(max)) was recorded. Survival curves were obtained using Kaplan-Meier analysis and compared using the log rank test, followed by multivariate analysis using the Cox proportional hazards model to assess the independent effects of International Prognostic Index (IPI) score (0-1 vs. 2-5), stage (stage I/II vs. stage III/IV), sex, DS (1-3 vs. 4-5), SUV(max), and change in SUV(max) on overall survival (OS) and progression-free survival (PFS). The mean (±SD) follow-up period was 32 mo (±21 mo). RESULTS: For 2-y OS, the following parameters were predictive: IPI score (P = 0.047), DS at mid- and end-treatment (P < 0.001), and SUV(max) at mid- and end-treatment (P < 0.001 and 0.045, respectively). For 2-y PFS, the following parameters were predictive: sex (P = 0.006), stage (P = 0.034), IPI score (P = 0.038), DS at mid- and end-treatment (P < 0.001 and 0.001, respectively), and SUV(max) at midtreatment (P = 0.001). Multivariate analysis showed DS on mid- and end-treatment scans to be the only significant independent predictor of both OS (P = 0.004 and 0.018, respectively) and PFS (P = 0.004 and 0.014, respectively). The 2-y estimate for OS and PFS was 81% and 62%, respectively, in patients with a DS of 1-3, compared with 17% in patients with a DS of 4-5 (P < 0.001 and 0.001, respectively). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the midtreatment DS for prediction of OS and PFS were 63%, 94%, 83%, 83%, and 83%, respectively. CONCLUSION: Midtreatment PET/CT is a valuable tool for early treatment response assessment in extranodal natural killer/T-cell lymphoma patients.

Radiation induced brain injury: assessment of white matter tracts in a pre-clinical animal model using diffusion tensor MR imaging.

We aim to study radiation induced white matter injury in a pre-clinical model using Diffusion tensor MR imaging (DTI). Nineteen 12-week old Sprague-Dawley rats were irradiated to the right hemisphere using a linear accelerator. The dose distribution map was coregistered to the DTI map to generate the actual radiation dose to each white matter tract. Rats underwent longitudinal DTI scans at five time points from 4 to 48 weeks post-radiation with histological evaluations. Fractional anisotropy (FA) of the external capsule, fornix, cerebral peduncle, anterior commissure, optic tract and optic nerve was evaluated. Radiation dose was highest at the ipsilateral external capsule and fornix (29.4 ± 1.3 and 29.8 ± 1.1 Gy, respectively). Optic nerve received 50 % dose to the external capsule and other white matter tracts received 80 % dose. Significantly lower FA was firstly found in the ipsilateral external capsule at 4 weeks post-radiation and in the ipsilateral fornix at 40 weeks post-radiation compared to the contralateral side. Significantly lower FA was found in contralateral optic nerve compared to ipsilateral optic nerve at 48 weeks post-radiation despite ipsilateral optic nerves receiving higher radiation dose than contralateral optic nerve (p = 0.021). No differences were found in other white matter regions until 48 weeks. Histology indicated demyelination, axonal degeneration and coagulative necrosis in all injured white matter. DTI can serve as a promising tool for assessment of radiation induced white matter injury and regional radiosensitivity of white matter tracts.

Utility of FDG PET/CT in the assessment of myeloid sarcoma.

OBJECTIVE: Myeloid sarcoma (MS) is a rare extramedullary manifestation of acute myeloid leukemia that often presents during remission or disease relapse. With awareness of this clinical entity and the appropriate clinical history, MS can be detected despite its nonspecific radiologic features. CONCLUSION: This article highlights the utility of (18)F-FDG PET/CT, which has high sensitivity in detecting early MS and provides a systemic overview of tumor burden, and its potential role in monitoring of treatment response.

Quantitative assessment of the cervical spinal cord damage in neuromyelitis optica using diffusion tensor imaging at 3 Tesla.

PURPOSE: To investigate whether quantitative MRI measures of cervical spinal cord white matter (WM) using diffusion tensor imaging (DTI) in neuromyelitis optica (NMO) differed from controls and correlated with clinical disability. MATERIALS AND METHODS: Ten referred patients and 12 healthy volunteers were imaged on a 3 Tesla scanner and patients were clinically assessed on the Expanded Disability Status Scale (EDSS). Two raters quantified DTI-derived indices from all participants, including fractional anisotropy (FA), mean diffusivity (MD), parallel diffusivity (lambda[parallel]) and perpendicular diffusivity (lambda[perpendicular]) at C1-C6 for lateral and dorsal columns. After the inter-rater reliability test, univariate correlations between DTI measures and disability were assessed using the Spearman's rho correlation coefficient. Multiple regression analysis was performed to investigate which DTI measures independently correlated with the clinical score. RESULTS: Statistical test results indicated high reliability of all DTI measurements between two raters. NMO patients showed reduced FA, increased MD and lambda[perpendicular] compared with controls while lambda[parallel] did not show any significant difference. The former three DTI metrics also showed significant correlations with disability scores, and especially FA was found to be sensitive to mild NMO (EDSS ≤ 3) CONCLUSION: FA is a potentially useful quantitative biomarker of otherwise normal appearing WM damage in NMO. Such damage is associated with clinical disability.

Assessment of glycosaminoglycan distribution in human lumbar intervertebral discs using chemical exchange saturation transfer at 3 T: feasibility and initial experience.

Recent studies have proposed that glycosaminoglycan chemical exchange saturation transfer (gagCEST) is associated with a loss of glycosaminoglycans (GAGs), which may be an initiating factor in intervertebral disc (IVD) degeneration. Despite its promising potential, this application has not been reported in human in vivo IVD studies because of the challenges of B(0) magnetic field inhomogeneity in gagCEST. This study aimed to evaluate the feasibility of quantifying CEST values in IVDs of healthy volunteers using a clinical 3 T scanner. A single-slice turbo spin echo sequence was used to quantify the CEST effect in various GAG phantoms and in IVDs of 12 volunteers. The phantom results indicated high correlation between gagCEST and GAG concentrations (R(2) = 0.95). With optimal B(0) inhomogeneity correction, in vivo CEST maps of IVDs showed robust contrast between the nucleus pulposus (NP) and the annulus fibrosus (AF) (p < 0.01), as well as higher signal in the central relative to the peripheral NP. In addition, a trend of decreasing CEST values from upper to lower disc levels was evident in NP. Our results demonstrate that in vivo gagCEST quantification in human lumbar IVDs is feasible at 3 T in combination with successful B(0) inhomogeneity correction, but without significant hardware modifications. Our initial findings suggest that it would be worthwhile to perform direct correlation studies between CEST and GAGs using cadaver samples, and to extend this novel technique to studies on patients with degenerative discs to better understand its distinct imaging features relative to conventional techniques.

Quantitative assessment of diffusion-weighted MR imaging in patients with primary rectal cancer: correlation with FDG-PET/CT.

PURPOSE: The aim of the study was to assess correlations between parameters on diffusion-weighted imaging and 2-deoxy-2-[(18)F]fluoro-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in rectal cancer. PROCEDURES: Thirty-three consecutive patients with pathologically confirmed rectal adenocarcinoma were included in this study. Apparent diffusion coefficient (ADC) maps were generated to calculate ADC(mean) (average ADC), ADC(min) (lowest ADC), tumor volume, and total diffusivity index (TDI). PET/CT exams were performed within 1 week of magnetic resonance imaging. Standardized uptake values (SUVs) were normalized to the injected FDG dose and body weight. SUV(max) (maximum SUV), SUV(mean) (average SUV), tumor volume, and total lesion glycolysis (TLG) were calculated using a 50% threshold. RESULTS: Significant negative correlations were found between ADC(min) and SUV(max) (r = -0.450, p = 0.009), and between ADC(mean) and SUV(mean) (r = -0.402, p = 0.020). A significant positive correlation was found between TDI and TLG (r = 0.634, p < 0.001). CONCLUSION: The significant negative correlations between ADC and SUV suggest an association between tumor cellularity and metabolic activity in primary rectal adenocarcinoma.

Mapping radiation dose distribution on the fractional anisotropy map: applications in the assessment of treatment-induced white matter injury.

We describe a method to map whole brain radiation dose distribution on to diffusion tensor MR (DT-MR) fractional anisotropy (FA) images and illustrate its applications for studying dose-effect relationships and regional susceptibility in two childhood medulloblastoma survivors. To determine the FA changes voxel-by-voxel in white matter, the post-treatment follow-up FA maps were coregistered to baseline pre-treatment FA maps and automatic segmentation for white matter was carried out. DeltaFA maps representing relative FA change in white matter were hence generated for visual inspection and quantitative analysis. The radiation dose distribution, calculated from radiotherapy plan and exported as images, was coregistered to baseline FA images. DT-MR imaging and processing noise was small with root mean square value of 1.49% for mean DeltaFA. We evaluated the mean DeltaFA changes of regions-of-interest according to radiation dose regions to provide an estimate of the dose-response and found increasing reduction in mean DeltaFA with increasing radiation dose up to 45 Gy after which there was a reversal in the mean FA trend and mean FA approached baseline value. We also found more severe mean FA reduction in the frontal lobes compared to the parietal lobes despite the same radiation dose, suggesting regional susceptibility in the frontal lobe, and mean FA increase in the brainstem after radiation in both patients. We conclude that the method described may be useful in estimating dose-effect relationships and studying regional susceptibility of the brain to radiation in medulloblastoma survivors.