CEST-MRI for body oncologic imaging: are we there yet?

Chemical exchange saturation transfer (CEST) MRI has gained recognition as a valuable addition to the molecular imaging and quantitative biomarker arsenal, especially for characterization of brain tumors. There is also increasing interest in the use of CEST-MRI for applications beyond the brain. However, its translation to body oncology applications lags behind those in neuro-oncology. The slower migration of CEST-MRI to non-neurologic applications reflects the technical challenges inherent to imaging of the torso. In this review, we discuss the application of CEST-MRI to oncologic conditions of the breast and torso (i.e., body imaging), emphasizing the challenges and potential solutions to address them. While data are still limited, reported studies suggest that CEST signal is associated with important histology markers such as tumor grade, receptor status, and proliferation index, some of which are often associated with prognosis and response to therapy. However, further technical development is still needed to make CEST a reliable clinical application for body imaging and establish its role as a predictive and prognostic biomarker.

Introduction to the COG Diagnostic Imaging Committee/SPR Oncology Committee White Papers: Rationale and methods.

Pediatric cancer is a rare disease. Because of this, many sites do not have experience providing imaging for specific tumor types. The Children's Oncology Group Diagnostic Imaging Committee and the Society for Pediatric Radiology Oncology Committee are comprised of radiologists with expertise in pediatric cancer imaging. Recently, this group endeavored to create a series of 23 White Papers designed to provide evidence-based imaging recommendations and minimum achievable imaging protocols. The purpose of this manuscript is to describe the methods employed in authoring the White Paper series.

Diagnostic errors in musculoskeletal oncology and possible mitigation strategies.

The objective of this paper is to explore sources of diagnostic error in musculoskeletal oncology and potential strategies for mitigating them using case examples. As musculoskeletal tumors are often obvious, the diagnostic errors in musculoskeletal oncology are frequently cognitive. In our experience, the most encountered cognitive biases in musculoskeletal oncologic imaging are as follows: (1) anchoring bias, (2) premature closure, (3) hindsight bias, (4) availability bias, and (5) alliterative bias. Anchoring bias results from failing to adjust an early impression despite receiving additional contrary information. Premature closure is the cognitive equivalent of "satisfaction of search." Hindsight bias occurs when we retrospectively overestimate the likelihood of correctly interpreting the examination prospectively. In availability bias, the radiologist judges the probability of a diagnosis based on which diagnosis is most easily recalled. Finally, alliterative bias occurs when a prior radiologist's impression overly influences the diagnostic thinking of another radiologist on a subsequent exam. In addition to cognitive biases, it is also important for radiologists to acknowledge their feelings when making a diagnosis to recognize positive and negative impact of affect on decision making. While errors decrease with radiologist experience, the lack of application of medical knowledge is often the primary source of error rather than a deficiency of knowledge, emphasizing the need to foster clinical reasoning skills and assist cognition. Possible solutions for reducing error exist at both the individual and the system level and include (1) improvement in knowledge and experience, (2) improvement in clinical reasoning and decision-making skills, and (3) improvement in assisting cognition.

Carbon-fiber-reinforced polyetheretherketone orthopedic implants in musculoskeletal and spinal tumors: imaging and clinical features.

Carbon-fiber-reinforced polyetheretherketone (CFR-PEEK) orthopedic implants are gaining popularity in oncologic applications as they offer many potential advantages over traditional metallic implants. From an imaging perspective, this instrumentation allows for improved evaluation of adjacent anatomic structures during radiography, computed tomography (CT), and magnetic resonance imaging (MRI). This results in improved postoperative surveillance imaging quality as well as easier visualization of anatomy for potential image-guided percutaneous interventions (e.g., pain palliation injections, or ablative procedures for local disease control). CFR-PEEK devices are also advantageous in radiation oncology treatment due to their decreased imaging artifact during treatment planning imaging and decreased dose perturbation during radiotherapy delivery. As manufacturing processes for CFR-PEEK materials continue to evolve and improve, potential orthopedic applications in the spine and appendicular skeleton increase. An understanding of the unique properties of CFR-PEEK devices and their impact on imaging is valuable to radiologists delivering care to orthopedic oncology patients in both the diagnostic and interventional settings. This multidisciplinary review aims to provide a comprehensive insight into the radiologic, surgical, and radiation oncology impact of these innovative devices.

A sigh of relief: vaccine-associated hypermetabolic lymphadenopathy following the third COVID-19 vaccine dose is short in duration and uncommonly interferes with the interpretation of [18F]FDG PET-CT studies performed in oncologic patients.

PURPOSE: The incidence of COVID-19 vaccine-associated hypermetabolic lymphadenopathy (VAHL) is high following the administration of the first and second BNT162b2 vaccine doses. The impact of this finding on [18F]FDG PET-CT interpretation and its correlation with the induced humoral immunity have been reported. Assuming the amnestic immune response is different following the third vaccine dose, we aimed to explore the incidence of VAHL over time after the third BNT162b2 dose administration, and its relevance to [18F]FDG PET-CT interpretation in oncologic patients. METHODS: A total of 179 consecutive oncologic patients that underwent [18F]FDG PET-CT after a third BNT162b2 vaccine dose were included. The presence of VAHL was assessed. On VAHL-positive scans, the SUVmax, number, location, and size of the "hot" nodes were recorded. The median time interval between vaccination and imaging was 8 (IQR, 5-14) days. RESULTS: The incidences of all-grade VAHL and grade 3-4 VAHL were 47.5% and 8.9%, respectively. VAHL was identified on 82.5% of studies performed within the first 5 days from vaccination. Grade 3-4 VAHL was observed on 28.1% of studies performed within the first 5 days from vaccination, but was not detected on studies performed more than 5 days from vaccination. Separation between VAHL and malignant lymphadenopathy was not possible in only 2 of the 179 study patients. On a multivariable logistic regression, independent predictors of grade 3-4 VAHL were short time interval between vaccination and imaging (Pv < 0.01), younger age (Pv < 0.01), and lower BMI (Pv = 0.03). CONCLUSION: VAHL is commonly identified on [18F]FDG PET-CT performed within the first 5 days from the third BNT162b2 vaccine dose administration. High-grade VAHL is unlikely to be observed on a scan performed 6 days or longer from vaccination, and is even less likely in older and obese patients.

Interventional Ultrasound in Dermatology: A Pictorial Overview Focusing on Cutaneous Melanoma Patients.

Cutaneous melanoma incidence is increasing worldwide, representing an aggressive tumor when evolving to the metastatic phase. High-resolution ultrasound (US) is playing a growing role in the assessment of newly diagnosed melanoma cases, in the locoregional staging prior to the sentinel lymph-node biopsy procedure, and in the melanoma patient follow-up. Additionally, US may guide a number of percutaneous procedures in the melanoma patients, encompassing diagnostic and therapeutic modalities. These include fine needle cytology, core biopsy, placement of presurgical guidewires, aspiration of lymphoceles and seromas, and electrochemotherapy.

Vascular Imaging in the Asymptomatic High-risk Cancer Population: A Role for Thrombosis Screening and Therapy Management.

OBJECTIVES: We retrospectively examined the venous thromboembolism (VTE) events diagnosed in the Prophylaxis of High-Risk Ambulatory Cancer Patients Study (PHACS), a multi-center randomized trial, to assess the value of screening vascular imaging for the diagnosis of incidental VTE in high-risk cancer patients. METHODS: A total of 117 asymptomatic cancer patients with a Khorana score ≥3 starting a new systemic chemotherapy regimen were enrolled in a prospective randomized control trial. Patients underwent baseline venous ultrasound (US) of the lower extremities (LEs) and screening contrast-enhanced chest computed tomography (CT). Those without preexisting VTE were then randomized into observation or dalteparin prophylaxis groups and were screened with serial US every 4 weeks for up to 12 weeks and imaged with contrast-enhanced chest CT at 12 weeks. Any additional imaging performed during the study period was also evaluated for VTE. RESULTS: Baseline prevalence of incidental VTE was 9% (n = 10) with 58% percent of VTEs diagnosed by screening US. Incidence of VTE in the randomized phase of the trial was 16% (n = 16) with 21% (n = 10) of patients in the control arm and 12% (n = 6) of patients in the dalteparin arm developing VTE, a non-significant 9% absolute risk reduction (HR = 0.69, 95% CI 0.23-1.89). Sixty-nine percent of these patients were asymptomatic with 31% of patients diagnosed by screening US. CONCLUSIONS: Adding screening US to routine oncologic surveillance CT in high-risk ambulatory cancer patients with a Khorana score ≥3 can lead to increased VTE detection, with potential for decreased morbidity, mortality, and health care spending.

Hypermetabolic lymphadenopathy following administration of BNT162b2 mRNA Covid-19 vaccine: incidence assessed by [18F]FDG PET-CT and relevance to study interpretation.

PURPOSE: Nationwide mass vaccination against Covid-19 started in Israel in late 2020. Soon we identified on [18F]FDG PET-CT studies vaccine-associated hypermetabolic lymphadenopathy (VAHL) in axillary or supraclavicular lymph nodes (ASLN) ipsilateral to the vaccination site. Sometimes, differentiation between the malignant and benign nature of the hypermetabolic lymphadenopathy (HLN) could not be made, and equivocal HLN (EqHL) was reported. The purpose of the study was to determine the overall incidence of VAHL after BNT162b2 vaccination and also its relevance to PET-CT interpretation in oncologic patients. METHODS: A total of 951 consecutive patients that underwent [18F]FDG PET-CT studies in our department were interviewed regarding the sites and dates of the vaccine doses. A total of 728 vaccinated patients (All-Vac group) were included: 346 received the first dose only (Vac-1 group) and 382 received the booster dose as well (Vac-2 group). Studies were categorized as no HLN, malignant-HLN (MHL), VAHL, or EqHL. In studies with VAHL, location, [18F]FDG-intensity uptake and nodes size were recorded. RESULTS: The incidences of HLN were 45.6%, 36.4%, and 53.9% in All-Vac, Vac-1, and Vac-2 groups, respectively. VAHL was reported in 80.1% of vaccinated patients with HLN. Lower incidences of VAHL were found during the first 5 days or in the third week after the first vaccine and beyond 20 days after the booster dose. In 49 of 332 (14.8%) vaccinated patients, we could not determine whether HLN was MHL or VAHL. Breast cancer and lymphoma were the leading diseases with EqHL. CONCLUSION: VAHL is frequently observed after BNT162b2 administration, more commonly and with higher intensity following the booster dose. To minimize false and equivocal reports in oncological patients, timing of [18F]FDG PET-CT should be based on the time intervals found to have a lower incidence of VAHL, and choice of vaccine injection site should be advised, mainly in patients where ASLN are a relevant site of tumor involvement.

Conspicuity of malignant pleural mesothelioma in contrast enhanced MDCT - arterial phase or late phase?

BACKGROUND: To determine if late phase is superior to arterial phase intraindividually regarding conspicuity of MPM in contrast enhanced chest MDCT. METHODS: 28 patients with MPM were included in this retrospective study. For all patients, chest CT in standard arterial phase (scan delay ca. 35 s) and abdominal CT in portal venous phase (scan delay ca. 70 s) was performed. First, subjective analysis of tumor conspicuity was done independently by two radiologists. Second, objective analysis was done by measuring Hounsfield units (HU) in tumor lesions and in the surrounding tissue in identical locations in both phases. Differences of absolute HUs in tumor lesions between phases and differences of contrast (HU in lesion - HU in surrounding tissue) between phases were determined. HU measurements were compared using paired t-test for related samples. Potential confounding effects by different technical and epidemiological parameters between phases were evaluated performing a multiple regression analysis. RESULTS: Subjective analysis: In all 28 patients and for both readers conspicuity of MPM was better on late phase compared to arterial phase. Objective analysis: MPM showed a significantly higher absolute HU in late phase (75.4 vs 56.7 HU, p < 0.001). Contrast to surrounding tissue was also significantly higher in late phase (difference of contrast between phases 18.5 HU, SD 10.6 HU, p < 0.001). Multiple regression analysis revealed contrast phase and tube voltage to be the only significant independent predictors for tumor contrast. CONCLUSIONS: In contrast enhanced chest-MDCT for MPM late phase scanning seems to provide better conspicuity and higher contrast to surrounding tissue compared to standard arterial phase scans.

COVID-19 Vaccination-Related Uptake on FDG PET/CT: An Emerging Dilemma and Suggestions for Management.

As mass COVID-19 vaccination is underway, radiologists are encountering transient FDG uptake in normal or enlarged axillary, supraclavicular, and cervical lymph nodes after ipsilateral deltoid vaccination. This phenomenon may confound interpretation in patients with cancer undergoing FDG PET/CT. In this article, we present our institutional approach for management of COVID-19 vaccine-related lymphadenopathy on FDG PET/CT according to early experience. We suggest performing PET/CT at least 2 weeks after vaccination in patients with a cancer for which interpretation is anticipated to be potentially impacted by the vaccination but optimally 4-6 weeks after vaccination given increased immunogenicity of mRNA vaccines and potentially longer time for resolution than lymphadenopathy after other vaccines. PET/CT should not be delayed when clinically indicated to be performed sooner. Details regarding vaccination should be collected at the time of PET/CT to facilitate interpretation. Follow-up recommendations for postvaccination lymphadenopathy are provided, considering the lymph node's morphology and likely clinical relevance. Consideration should be given to administering the vaccine in the arm contralateral to a unilateral cancer to avoid confounding FDG uptake on the side of cancer. Our preliminary experience and suggested institutional approach should guide radiologists in management of patients with cancer undergoing PET/CT after COVID-19 vaccination.

Cancer Clinical Trials: What Every Radiologist Wants to Know but Is Afraid to Ask.

OBJECTIVE. The purpose of this article is to provide radiologists with a guide to the fundamental principles of oncology clinical trials. The review summarizes the evolution and structure of modern clinical trials with an emphasis on the relevance of clinical trials in the field of oncologic imaging. CONCLUSION. Understanding the structure and clinical relevance of modern clinical trials is beneficial for radiologists in the field of oncologic imaging.

CAR T-Cell Therapy: An Update for Radiologists.

Chimeric antigen receptor-engineered (CAR) T-cell therapy is a promising novel immunotherapy that has the potential to revolutionize cancer treatment. Four CAR T-cell therapies have received FDA approval within the last 5 years, and the role of CAR T cells is anticipated to continue to evolve and expand. However, various aspects of CAR T-cell therapies remain poorly understood, and the therapies are associated with severe side effects, including cytokine release syndrome and immune effector cell-associated neurotoxicity, which require prompt diagnosis and intervention. The purposes of this review are to describe the role of imaging in diagnosing and monitoring toxicities from CAR T-cell therapies and explore the use of various imaging techniques, including PET/CT with novel radiotracers, to predict and assess treatment response and adverse effects. It is important for radiologists to recognize the imaging findings associated with each syndrome and to recognize the typical and atypical treatment response patterns associated with CAR T-cell therapy. Given the expected increase in use of CAR T cells in the near future, radiologists should familiarize themselves with the imaging findings encountered in these novel therapies so that they can provide comprehensive and up-to-date guidance for clinical management.

[Chemical exchange saturation transfer (CEST) : Magnetic resonance imaging in diagnostic oncology]. / "Chemical exchange saturation transfer" (CEST) : Magnetresonanztomographie in der onkologischen Diagnostik.

BACKGROUND: Contrast generation by chemical exchange saturation transfer (CEST) is a recently emerging magnetic resonance imaging (MRI) research field with high clinical potential. METHODS: This review covers the methodological principles and summarizes the clinical experience of CEST imaging studies in diagnostic oncology performed to date. RESULTS AND CONCLUSION: CEST enables the detection of lowly concentrated metabolites, such as peptides and glucose, through selective saturation of metabolite-bound protons and subsequent magnetization transfer to free water. This technology yields additional information about metabolic activity and the tissue microenvironment without the need for conventional contrast agents or radioactive tracers. Various studies, mainly conducted in patients with neuro-oncolgic diseases, suggest that this technology may aid to assess tumor malignancy as well as therapeutic response prior to and in the first follow-up after intervention. KEY POINTS: CEST-MRI enables the indirect detection of metabolites without radioactive tracers or contrast agents. Clinical experience exists especially in the setting of neuro-oncologic imaging. In oncologic imaging, CEST-MRI may improve assessment of prognosis and therapy response.

Multimodality oncologic evaluation of superficial neck and facial lymph nodes.

Involvement of lymph nodes in patients with head and neck cancers impacts treatment and prognosis. Head and neck lymph nodes are comprised of superficial and deep groups which are interconnected. The deep lymph nodes, predominantly centered along internal jugular veins, are very well-known to radiologists and clinicians. However, superficial lymph nodes that drain lymph from the scalp, face, and neck are much less recognized. Here, we describe the anatomic and imaging features of these superficial lymph nodes on CT, MRI, and PET in oncologic settings.

MR Denoising Increases Radiomic Biomarker Precision and Reproducibility in Oncologic Imaging.

Several noise sources, such as the Johnson-Nyquist noise, affect MR images disturbing the visualization of structures and affecting the subsequent extraction of radiomic data. We evaluate the performance of 5 denoising filters (anisotropic diffusion filter (ADF), curvature flow filter (CFF), Gaussian filter (GF), non-local means filter (NLMF), and unbiased non-local means (UNLMF)), with 33 different settings, in T2-weighted MR images of phantoms (N = 112) and neuroblastoma patients (N = 25). Filters were discarded until the most optimal solutions were obtained according to 3 image quality metrics: peak signal-to-noise ratio (PSNR), edge-strength similarity-based image quality metric (ESSIM), and noise (standard deviation of the signal intensity of a region in the background area). The selected filters were ADFs and UNLMs. From them, 107 radiomics features preservation at 4 progressively added noise levels were studied. The ADF with a conductance of 1 and 2 iterations standardized the radiomic features, improving reproducibility and quality metrics.

Decoding the Genomic Report for Radiologists.

OBJECTIVE. The purpose of this review is to provide a guide for radiologists that explains the language and format of modern genomic reports and summarizes the relevance of this information for modern oncologic imaging. CONCLUSION. Genomic testing plays a critical role in guiding oncologic therapies in the age of targeted treatments. Understanding and interpreting genomic reports is a valuable skill for radiologists involved with oncologic imaging interpretation.

The Role of Imaging and Systemic Treatments in Myeloma: A Primer for Radiologists.

OBJECTIVE. The purpose of this article is to provide an up-to-date guide for radiologists on imaging and systemic therapies in myeloma and related conditions, with a focus on radiologic findings for diagnosis and treatment response assessment. CONCLUSION. Knowledge of the unique imaging presentations of myeloma is highly useful for radiologists. An understanding of the utility of different imaging modalities and the systemic therapies used in multiple myeloma is also critical in the realm of oncologic imaging.

A Radiologist's Guide to the Changing Treatment Paradigm of Advanced Non-Small Cell Lung Cancer: The ASCO 2018 Molecular Testing Guidelines and Targeted Therapies.

OBJECTIVE. The purpose of this article is to provide an imaging-based guide of the modern genomic classifications and targeted therapies for advanced non-small cell lung cancer (NSCLC) with an emphasis on the relevance of the 2018 American Society of Clinical Oncology molecular testing guidelines for radiologists. CONCLUSION. Knowledge of the radiologic relevance of lung cancer driver mutations and modern targeted agents is essential for imaging interpretation of advanced NSCLC in the modern age of precision medicine.

Primary Mediastinal Large B-Cell Lymphoma: A Review for Radiologists.

OBJECTIVE. The purpose of this article is to provide a primer for radiologists focused on integrating the radiologic, pathologic, and clinical features of primary mediastinal large B-cell lymphoma (PMLBCL). CONCLUSION. PMLBCL is a unique subtype of lymphoma that poses diagnostic and therapeutic challenges to the fields of radiology and oncology. Knowledge of this distinctive clinical-pathologic entity and its associated imaging and clinical features is critical for radiologists.

Repeatability and reproducibility of cerebral 23Na imaging in healthy subjects.

BACKGROUND: Initial reports of 23Na magnetic resonance imaging (MRI) date back to the 1970s. However, methodological challenges of the technique hampered its widespread adoption for many years. Recent technical developments have overcome some of these limitations and have led to more optimal conditions for 23Na-MR imaging. In order to serve as a reliable tool for the assessment of clinical stroke or brain tumor patients, we investigated the repeatability and reproducibility of cerebral sodium (23Na) imaging in healthy subjects. METHODS: In this prospective, IRB approved study 12 consecutive healthy volunteers (8 female, age 31 ± 8.3) underwent three cerebral 23Na-MRI examinations at 3.0 T (TimTrio, Siemens Healthineers) distributed between two separate visits with an 8 day interval. For each scan a T1w MP-RAGE sequence for anatomical referencing and a 3D-density-adapted, radial GRE-sequence for 23Na-imaging were acquired using a dual-tuned (23Na/1H) head-coil. On 1 day, these scans were repeated consecutively; on the other day, the scans were performed once. 23Na-sequences were reconstructed according to the MP-RAGE sequence, allowing direct cross-referencing of ROIs. Circular ROIs were placed in predetermined anatomic regions: gray and white matter (GM, WM), head of the caudate nucleus (HCN), pons, and cerebellum. External 23Na-reference phantoms were used to calculate the tissue sodium content. RESULTS: Excellent correlation was found between repeated measurements on the same day (r2 = 0.94), as well as on a different day (r2 = 0.86). No significant differences were found based on laterality other than in the HCN (63.1 vs. 58.7 mmol/kg WW on the right (p = 0.01)). Pronounced inter-individual differences were identified in all anatomic regions. Moderate to good correlation (0.310 to 0.701) was found between the readers. CONCLUSION: Our study has shown that intra-individual 23Na-concentrations in healthy subjects do not significantly differ after repeated scans on the same day and a pre-set time interval. This confirms the repeatability and reproducibility of cerebral 23Na-imaging. However, with manual ROI placement in predetermined anatomic landmarks, fluctuations in 23Na-concentrations can be observed.