Preoperative 11 C-Methionine PET-MRI in Pediatric Infratentorial Tumors.

PURPOSE: MRI is the main imaging modality for pediatric brain tumors, but amino acid PET can provide additional information. Simultaneous PET-MRI acquisition allows to fully assess the tumor and lower the radiation exposure. Although symptomatic posterior fossa tumors are typically resected, the patient management is evolving and will benefit from an improved preoperative tumor characterization. We aimed to explore, in children with newly diagnosed posterior fossa tumor, the complementarity of the information provided by amino acid PET and MRI parameters and the correlation to histopathological results. PATIENTS AND METHODS: Children with a newly diagnosed posterior fossa tumor prospectively underwent a preoperative 11 C-methionine (MET) PET-MRI. Images were assessed visually and semiquantitatively. Using correlation, minimum apparent diffusion coefficient (ADC min ) and contrast enhancement were compared with MET SUV max . The diameter of the enhancing lesions was compared with metabolic tumoral volume. Lesions were classified according to the 2021 World Health Organization (WHO) classification. RESULTS: Ten children were included 4 pilocytic astrocytomas, 2 medulloblastomas, 1 ganglioglioma, 1 central nervous system embryonal tumor, and 1 schwannoma. All lesions showed visually increased MET uptake. A negative moderate correlation was found between ADC min and SUV max values ( r = -0.39). Mean SUV max was 3.8 (range, 3.3-4.2) in WHO grade 4 versus 2.5 (range, 1.7-3.0) in WHO grade 1 lesions. A positive moderate correlation was found between metabolic tumoral volume and diameter values ( r = 0.34). There was no correlation between SUV max and contrast enhancement intensity ( r = -0.15). CONCLUSIONS: Preoperative 11 C-MET PET and MRI could provide complementary information to characterize pediatric infratentorial tumors.

Baseline Characteristics and Use of Pretherapeutic 18 F-Fluorodeoxyglucose-PET for Pancreatic Cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal malignancy. Surgical resection is the only curative modality combined with neoadjuvant chemotherapy to improve survival. Given the limitations of traditional responses such as cross-sectional imaging (CT/MRI) or tumor markers, carbohydrate antigen 19-9 (CA19-9), the 2023 National Comprehensive Cancer Network guidelines included 18 F-fluorodeoxyglucose (FDG)-PET as an adjunct to assess response to neoadjuvant chemotherapy. There are common misconceptions on the metabolic activity (tumor avidity) in PDAC so we aimed to describe the baseline characteristics and use of FDG-PET in a cohort of treatment-naive patients with PDAC. STUDY DESIGN: A single-center retrospective study was conducted capturing all biopsy-proven, treatment-naive patients with PDAC who underwent either baseline FDG-PET/CT or FDG-PET/MRI imaging between 2008 and 2023. Baseline FDG-PET characteristics were collected, including primary tumors' maximum standardized uptake value defined as metabolic activity (FDG uptake) of tumor compared with surrounding pancreatic parenchymal background, and the identification of extrapancreatic metastatic disease. RESULTS: We identified 1,095 treatment-naive patients with PDAC who underwent baseline FDG-PET imaging at diagnosis. CA19-9 was elevated in 76% of patients. Overall, 96.3% (1,054) of patients had FDG-avid tumors with a median maximum standardized uptake value of 6.4. FDG-PET also identified suspicious extrapancreatic metastatic lesions in 50% of patients, with a higher proportion (p < 0.001) in PET/MRI (59.9%) vs PET/CT (44.3%). After controlling for CA19-9 elevation, PET/MRI was superior in detection of extrapancreatic lesions compared with PET/CT. CONCLUSIONS: FDG-PET has significant use in PDAC as a baseline imaging modality earlier neoadjuvant therapy given the majority of tumors are FDG-avid. FDG-PET can identify additional extrapancreatic suspicious lesions allowing for optimal initial staging, with PET/MRI having increased sensitivity over PET/CT.

PET/SPECT/Spectral-CT/CBCT imaging in a small-animal radiation therapy platform: A Monte Carlo study-Part II: Biologically guided radiotherapy.

BACKGROUND: This study addresses the technical gap between clinical radiation therapy (RT) and preclinical small-animal RT, hindering the comprehensive validation of innovative clinical RT approaches in small-animal models of cancer and the translation of preclinical RT studies into clinical practices. PURPOSE: The main aim was to explore the feasibility of biologically guided RT implemented within a small-animal radiation therapy (SART) platform, with integrated quad-modal on-board positron emission tomography (PET), single-photon emission computed tomography, photon-counting spectral CT, and cone-beam CT (CBCT) imaging, in a Monte Carlo model as a proof-of-concept. METHODS: We developed a SART workflow employing quad-modal imaging guidance, integrating multimodal image-guided RT and emission-guided RT (EGRT). The EGRT algorithm was outlined using positron signals from a PET radiotracer, enabling near real-time adjustments to radiation treatment beams for precise targeting in the presence of a 2-mm setup error. Molecular image-guided RT, incorporating a dose escalation/de-escalation scheme, was demonstrated using a simulated phantom with a dose painting plan. The plan involved delivering a low dose to the CBCT-delineated planning target volume (PTV) and a high dose boosted to the highly active biological target volume (hBTV) identified by the 18F-PET image. Additionally, the Bayesian eigentissue decomposition method illustrated the quantitative decomposition of radiotherapy-related parameters, specifically iodine uptake fraction and virtual noncontrast (VNC) electron density, using a simulated phantom with Kidney1 and Liver2 inserts mixed with an iodine contrast agent at electron fractions of 0.01-0.02. RESULTS: EGRT simulations generated over 4,000 beamlet responses in dose slice deliveries and illustrated superior dose coverage and distribution with significantly lower doses delivered to normal tissues, even with a 2-mm setup error introduced, demonstrating the robustness of the novel EGRT scheme compared to conventional image-guided RT. In the dose-painting plan, doubling the dose to the hBTV while maintaining a low dose for the PTV resulted in an organ-at-risk (OAR) dose comparable to the low-dose treatment for the PTV alone. Furthermore, the decomposition of radiotherapy-related parameters in Kidney1 and Liver2 inserts, including iodine uptake fractions and VNC electron densities, exhibited average relative errors of less than 1.0% and 2.5%, respectively. CONCLUSIONS: The results demonstrated the successful implementation of biologically guided RT within the proposed quad-model image-guided SART platform, with potential applications in preclinical RT and adaptive RT studies.

68Ga-RM2 PET-MRI versus MRI alone for evaluation of patients with biochemical recurrence of prostate cancer: a single-centre, single-arm, phase 2/3 imaging trial.

BACKGROUND: National Comprehensive Cancer Network guidelines include prostate-specific membrane antigen (PSMA)-targeted PET for detection of biochemical recurrence of prostate cancer. However, targeting a single tumour characteristic might not be sufficient to reflect the full extent of disease. Gastrin releasing peptide receptors (GRPR) have been shown to be overexpressed in prostate cancer. In this study, we aimed to evaluate the diagnostic performance of the GRPR-targeting radiopharmaceutical 68Ga-RM2 in patients with biochemical recurrence of prostate cancer. METHODS: This single-centre, single-arm, phase 2/3 trial was done at Stanford University (USA). Adult patients (aged ≥18 years) with biochemical recurrence of prostate cancer, a Karnofsky performance status of 50 or higher, increasing prostate-specific antigen concentration 0·2 ng/mL or more after prostatectomy or 2 ng/mL or more above nadir after radiotherapy, and non-contributory conventional imaging (negative CT or MRI, and bone scan) were eligible. All participants underwent 68Ga-RM2 PET-MRI. The primary outcome was the proportion of patients with PET-positive findings on 68Ga-RM2 PET-MRI compared with MRI alone after initial therapy, at a per-patient and per-lesion level. The primary outcome would be considered met if at least 30% of patients had one or more lesions detected by 68Ga-RM2 PET-MRI and the detection by 68Ga-RM2 PET-MRI was significantly greater than for MRI. Each PET scan was interpreted by three independent masked readers using a standardised evaluation criteria. This study is registered with ClinicalTrials.gov, NCT02624518, and is complete. FINDINGS: Between Dec 12, 2015, and July 27, 2021, 209 men were screened for eligibility, of whom 100 were included in analyses. Median follow-up was 49·3 months (IQR 36·7-59·2). The primary endpoint was met; 68Ga-RM2 PET-MRI was positive in 69 (69%) patients and MRI alone was positive in 40 (40%) patients (p<0·0001). In the per-lesion analysis 68Ga-RM2 PET-MRI showed significantly higher detection rates than MRI alone (143 vs 96 lesions; p<0·0001). No grade 1 or worse events were reported. INTERPRETATION: 68Ga-RM2 PET-MRI showed better diagnostic performance than MRI alone in patients with biochemical recurrence of prostate cancer. Further prospective comparative studies with PSMA-targeted PET are needed to gain a better understanding of GRPR and PSMA expression patterns in these patients. FUNDING: The US Department of Defense.

A Prospective Registry Study of 68Ga-DOTATATE PET/CT Incorporation Into Treatment Planning of Intracranial Meningiomas.

PURPOSE: The current standard for meningioma treatment planning involves magnetic resonance imaging-based guidance. Somatostatin receptor ligands such as 68Ga-DOTATATE are being explored for meningioma treatment planning due to near-universal expression of somatostatin receptors 1 and 2 in meningioma tissue. We hypothesized that 68Ga-DOTATATE positron emission tomography (PET)-guided treatment management for patients with meningiomas is safe and effective and can identify which patients benefit most from adjuvant radiation therapy. METHODS AND MATERIALS: A single-institution prospective registry study was created for inclusion of patients with intracranial meningiomas who received a 68Ga-DOTATATE PET/CT to assist with radiation oncologist decision making. Patients who received a PET scan from January 1, 2018, to February 25, 2022, were eligible for inclusion. RESULTS: Of the 60 patients included, 40%, 47%, and 5% had World Health Organization grades 1, 2, and 3 meningiomas, respectively, and 8% (5 patients) had no grade assigned. According to Radiation Therapy Oncology Group 0539 criteria, 22%, 72%, and 7% were categorized as high, intermediate, and low risk, respectively. After completing their PET scans, 48 patients, 11 patients, and 1 patient proceeded with radiation therapy, observation, and redo craniotomy, respectively. The median follow-up for the entire cohort was 19.5 months. Of the 3 patients (5%) who experienced local failure between 9.2 and 28.5 months after diagnosis, 2 had PET-avid disease in their postoperative cavity and elected for observation before recurrence, and 1 high-risk patient with multifocal disease experienced local failure 2 years after a second radiation course and multiple previous recurrences. Notably, 5 patients did not have any local PET uptake and were observed; none of these patients experienced recurrence. Only 1 grade 3 toxicity was attributed to PET-guided radiation. CONCLUSIONS: This study examined one of the largest known populations of patients with intracranial meningiomas followed by physicians who used 68Ga-DOTATATE PET-guided therapy. Incorporating 68Ga-DOTATATE PET into future trials may assist with clinician decision making and improve patient outcomes.

Diagnostic Accuracy of MR Spectroscopic Imaging and 18F-FET PET for Identifying Glioma: A Biopsy-Controlled Hybrid PET/MRI Study.

Contrast-enhanced MRI is the method of choice for brain tumor diagnostics, despite its low specificity for tumor tissue. This study compared the contribution of MR spectroscopic imaging (MRSI) and amino acid PET to improve the detection of tumor tissue. Methods: In 30 untreated patients with suspected glioma, O-(2-[18F]fluoroethyl)-l-tyrosine (18F-FET) PET; 3-T MRSI with a short echo time; and fluid-attenuated inversion recovery, T2-weighted, and contrast-enhanced T1-weighted MRI were performed for stereotactic biopsy planning. Serial samples were taken along the needle trajectory, and their masks were projected to the preoperative imaging data. Each sample was individually evaluated neuropathologically. 18F-FET uptake and the MRSI signals choline (Cho), N-acetyl-aspartate (NAA), creatine, myoinositol, and derived ratios were evaluated for each sample and classified using logistic regression. The diagnostic accuracy was evaluated by receiver operating characteristic analysis. Results: On the basis of the neuropathologic evaluation of tissue from 88 stereotactic biopsies, supplemented with 18F-FET PET and MRSI metrics from 20 areas on the healthy-appearing contralateral hemisphere to balance the glioma/nonglioma groups, 18F-FET PET identified glioma with the highest accuracy (area under the receiver operating characteristic curve, 0.89; 95% CI, 0.81-0.93; threshold, 1.4 × background uptake). Among the MR spectroscopic metabolites, Cho/NAA normalized to normal brain tissue showed the highest diagnostic accuracy (area under the receiver operating characteristic curve, 0.81; 95% CI, 0.71-0.88; threshold, 2.2). The combination of 18F-FET PET and normalized Cho/NAA did not improve the diagnostic performance. Conclusion: MRI-based delineation of gliomas should preferably be supplemented by 18F-FET PET.

Asymmetry of thalamic hypometabolism on FDG-PET/CT in neurofibromatosis type 1: Association with peripheral tumor burden.

BACKGROUND AND PURPOSE: Thalamic hypometabolism is a consistent finding in brain PET with F-18 fluorodeoxyglucose (FDG) in patients with neurofibromatosis type 1 (NF1). However, the pathophysiology of this metabolic alteration is unknown. We hypothesized that it might be secondary to disturbance of peripheral input to the thalamus by NF1-characteristic peripheral nerve sheath tumors (PNSTs). To test this hypothesis, we investigated the relationship between thalamic FDG uptake and the number, volume, and localization of PNSTs. METHODS: This retrospective study included 22 adult NF1 patients (41% women, 36.2 ± 13.0 years) referred to whole-body FDG-PET/contrast-enhanced CT for suspected malignant transformation of PNSTs and 22 sex- and age-matched controls. Brain FDG uptake was scaled voxelwise to the individual median uptake in cerebellar gray matter. Bilateral mean and left-right asymmetry of thalamic FDG uptake were determined using a left-right symmetric anatomical thalamus mask. PNSTs were manually segmented in contrast-enhanced CT. RESULTS: Thalamic FDG uptake was reduced in NF1 patients by 2.0 standard deviations (p < .0005) compared to controls. Left-right asymmetry was increased by 1.3 standard deviations (p = .013). Thalamic hypometabolism was higher in NF1 patients with ≥3 PNSTs than in patients with ≤2 PNSTs (2.6 vs. 1.6 standard deviations, p = .032). The impact of the occurrence of paraspinal/paravertebral PNSTs and of the mean PNST volume on thalamic FDG uptake did not reach statistical significance (p = .098 and p = .189). Left-right asymmetry of thalamic FDG uptake was not associated with left-right asymmetry of PNST burden (p = .658). CONCLUSIONS: This study provides first evidence of left-right asymmetry of thalamic hypometabolism in NF1 and that it might be mediated by NF1-associated peripheral tumors.

Post-ictal changes presenting as late pseudoprogression on MRI and PET in a patient with diffuse glioma: Case report and brief literature review.

Following completion of adjuvant radiation and chemotherapy imaging surveillance forms a major role in the management of diffuse gliomas. The primary role of imaging is to detect recurrences earlier than clinical symptomatology. Magnetic resonance imaging (MRI) is considered the gold standard in follow-up protocols owing to better soft tissue delineation and multiparametric nature. True recurrence can often mimic treatment-related changes, it is of paramount importance to differentiate between the two entities as the clinical course is divergent. Addition of functional sequences like perfusion, spectroscopy and metabolic imaging can provide further details into the microenvironment. In equivocal cases, a follow-up short interval imaging might be obtained to settle the diagnostic dilemma. Here, we present a patient with diagnosis of recurrent oligodendroglioma treated with adjuvant chemoradiation, presenting with seizures five years post-completion of chemotherapy for recurrence. On MRI, subtle new onset gyral thickening of the left frontal region with mild increase in perfusion and patchy areas of raised choline. FET-PET (fluoro-ethyltyrosine) showed an increased tumour-to-white matter (T/Wm) ratio favouring tumour recurrence. Based on discussion in a multi-disciplinary joint clinic, short interval follow-up MRI was undertaken at two months showing decrease in gyral thickening and resolution of enhancing areas in left frontal lobe. Repeat imaging one year later demonstrated stable disease status without further new imaging findings. Given the changes resolving completely without any anti-tumoral intervention, we conclude this to be peri-ictal pseudoprogression, being the second such case described in India.

A simulation of a high-resolution cadmium zinc telluride positron emission tomography system.

BACKGROUND: A CZT (cadmium zinc telluride) PET (positron emission tomography) system is being developed at Stanford University. CZT has the promise of outperforming scintillator-based systems in energy and spatial resolution but has relatively poor coincidence timing resolution. PURPOSE: To supplement GATE (GEANT 4 Application for Emission Tomography) simulations with charge transport and electronics modeling for a high-resolution CZT PET system. METHODS: A conventional GATE simulation was supplemented with electron-hole transport modeling and experimentally measured single detector energy resolution to improve the system-level understanding of a CZT high-resolution PET system in development at Stanford University. The modeling used GATE hits data and applied charge transport in the crystal and RC-CR processing of the simulated signals to model the electronics, including leading-edge discriminators and peak pick-off. Depth correction was also performed on the simulation data. Experimentally acquired data were used to determine energy resolution parameters and were compared to simulation data. RESULTS: The distributions of the coincidence timing, anode energy, and cathode energy are consistent with experimental data. Numerically, the simulation achieved 153 ns FWHM coincidence time resolution (CTR), which is of the same order of magnitude as the raw 210 ns CTR previously found experimentally. Further, the anode energy resolution was found to be 5.9% FWHM (full width at half maximum) at 511 keV in the simulation, which is between the experimental value found for a single crystal of 3% and the value found for the dual-panel setup of 8.02%, after depth correction. CONCLUSIONS: Developing this advanced simulation improves upon the limitations of GATE for modeling semiconductor PET systems and provides a means for deeper analysis of the coincidence timing resolution and other complementary electron-hole dependent system parameters.

Effects of de-facing software mri_reface on utility of imaging biomarkers used in Alzheimer's disease research.

Brain imaging research studies increasingly use "de-facing" software to remove or replace facial imagery before public data sharing. Several works have studied the effects of de-facing software on brain imaging biomarkers by directly comparing automated measurements from unmodified vs de-faced images, but most research brain images are used in analyses of correlations with cognitive measurements or clinical statuses, and the effects of de-facing on these types of imaging-to-cognition correlations has not been measured. In this work, we focused on brain imaging measures of amyloid (A), tau (T), neurodegeneration (N), and vascular (V) measures used in Alzheimer's Disease (AD) research. We created a retrospective sample of participants from three age- and sex-matched clinical groups (cognitively unimpaired, mild cognitive impairment, and AD dementia, and we performed region- and voxel-wise analyses of: hippocampal volume (N), white matter hyperintensity volume (V), amyloid PET (A), and tau PET (T) measures, each from multiple software pipelines, on their ability to separate cognitively defined groups and their degrees of correlation with age and Clinical Dementia Rating (CDR)-Sum of Boxes (CDR-SB). We performed each of these analyses twice: once with unmodified images and once with images de-faced with leading de-facing software mri_reface, and we directly compared the findings and their statistical strengths between the original vs. the de-faced images. Analyses with original and with de-faced images had very high agreement. There were no significant differences between any voxel-wise comparisons. Among region-wise comparisons, only three out of 55 correlations were significantly different between original and de-faced images, and these were not significant after correction for multiple comparisons. Overall, the statistical power of the imaging data for AD biomarkers was almost identical between unmodified and de-faced images, and their analyses results were extremely consistent.

Automated Brain Tumor Detection and Segmentation for Treatment Response Assessment Using Amino Acid PET.

Evaluation of metabolic tumor volume (MTV) changes using amino acid PET has become an important tool for response assessment in brain tumor patients. MTV is usually determined by manual or semiautomatic delineation, which is laborious and may be prone to intra- and interobserver variability. The goal of our study was to develop a method for automated MTV segmentation and to evaluate its performance for response assessment in patients with gliomas. Methods: In total, 699 amino acid PET scans using the tracer O-(2-[18F]fluoroethyl)-l-tyrosine (18F-FET) from 555 brain tumor patients at initial diagnosis or during follow-up were retrospectively evaluated (mainly glioma patients, 76%). 18F-FET PET MTVs were segmented semiautomatically by experienced readers. An artificial neural network (no new U-Net) was configured on 476 scans from 399 patients, and the network performance was evaluated on a test dataset including 223 scans from 156 patients. Surface and volumetric Dice similarity coefficients (DSCs) were used to evaluate segmentation quality. Finally, the network was applied to a recently published 18F-FET PET study on response assessment in glioblastoma patients treated with adjuvant temozolomide chemotherapy for a fully automated response assessment in comparison to an experienced physician. Results: In the test dataset, 92% of lesions with increased uptake (n = 189) and 85% of lesions with iso- or hypometabolic uptake (n = 33) were correctly identified (F1 score, 92%). Single lesions with a contiguous uptake had the highest DSC, followed by lesions with heterogeneous, noncontiguous uptake and multifocal lesions (surface DSC: 0.96, 0.93, and 0.81 respectively; volume DSC: 0.83, 0.77, and 0.67, respectively). Change in MTV, as detected by the automated segmentation, was a significant determinant of disease-free and overall survival, in agreement with the physician's assessment. Conclusion: Our deep learning-based 18F-FET PET segmentation allows reliable, robust, and fully automated evaluation of MTV in brain tumor patients and demonstrates clinical value for automated response assessment.

Bone Metastases Detection in Patients with Breast Cancer: Does Bone Scintigraphy Add Information to PET/CT?

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) has become in recent years a tool for breast cancer (BC) staging. However, its accuracy to detect bone metastases is classically considered inferior to bone scintigraphy (BS). The purpose of this work is to compare the effectiveness of bone metastases detection between PET/CT and BS. MATERIALS AND METHODS: Prospective study of 410 female patients treated in a Comprehensive Cancer Center between 2014 and 2020 that performed PET/CT and BS for staging purposes. The image analysis was performed by 2 senior nuclear medicine physicians. The comparison was performed based on accuracy, sensitivity, and specificity on a patient and anatomical region level and was assessed using McNemar's Test. An average ROC was calculated for the anatomical region analysis. RESULTS: PET/CT presented higher values of accuracy and sensitivity (98.0% and 93.83%), surpassing BS (95.61% and 81.48%) in detecting bone disease. There was a significant difference in favor of PET/CT (sensitivity 93.83% vs. 81.48%), however, there is no significant difference in eliminating false positives (specificity 99.09% vs. 99.09%). PET/CT presented the highest accuracy and sensitivity values for most of the bone segments, only surpassed by BS for the cranium. There was a significant difference in favor of PET/CT in the upper limb, spine, thorax (sternum) and lower limb (pelvis and sacrum), and in favor of BS in the cranium. The ROC showed that PET/CT has a higher sensitivity and consistency across the bone segments. CONCLUSION: With the correct imaging protocol, PET/CT does not require BS for patients with BC staging.

Diagnostic Performance of Response Assessment FDG-PET/CECT in HNSCC Treated With Definitive Radio(chemo)therapy Using NI-RADS.

OBJECTIVE: To assess the diagnostic performance of response assessment 18F-fluorodeoxyglucose positron emission tomography/contrast-enhanced computed tomography (FDG-PET/CECT) following definitive radio(chemo)therapy in head and neck squamous cell carcinoma (HNSCC) using Neck Imaging Reporting and Data System (NI-RADS). STUDY DESIGN: A retrospective analysis from a prospectively maintained dataset. SETTING: Tertiary-care comprehensive cancer center in a low-middle-income country. METHODS: Adults with newly diagnosed, biopsy-proven, nonmetastatic HNSCC treated with definitive radio(chemo)therapy were included. Posttreatment response assessment FDG-PET/CECT scans were retrospectively assigned NI-RADS categories (1-3) for the primary site, neck, and both sites combined. Locoregional recurrence occurring within 2-years was defined as the event of interest. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were calculated. Locoregional control stratified by NI-RADS categories was computed with the Kaplan-Meier method and compared using the log-rank test. RESULTS: Posttreatment FDG-PET/CECT scans were available in 190 patients constituting the present study cohort. Sensitivity, specificity, PPV, NPV, and overall accuracy of the NI-RADS template for the primary site was 73.5%, 81.4%, 46.3%, 93.4%, and 80.0%, respectively. Similar metrics for the neck were 72.7%, 87.5%, 43.2%, 96.1%, and 85.8%, respectively. Combining primary site and neck, the corresponding metrics of diagnostic accuracy were 84.4%, 69.7%, 46.3%, 93.5%, and 73.2%, respectively. At a median follow-up of 40 months, Kaplan-Meier estimates of 2-year locoregional control were significantly higher for NI-RADS category 1 (94.2%) compared to NI-RADS category 2 (69.4%) and category 3 (20.4%), respectively (stratified log-rank p < .0001). CONCLUSION: FDG-PET/CECT using the NI-RADS template is associated with good diagnostic performance and prognostic utility in HNSCC treated with definitive radio(chemo)therapy.

Study of compatibility between a 3T MR system and detector modules for a second-generation RF-penetrable TOF-PET insert for simultaneous PET/MRI.

BACKGROUND: Simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) has shown promise in acquiring complementary multiparametric information of disease. However, designing these hybrid imaging systems is challenging due to the propensity for mutual interference between the PET and MRI subsystems. Currently, there are integrated PET/MRI systems for clinical applications. For neurologic imaging, a brain-dedicated PET insert provides superior spatial resolution and sensitivity compared to body PET scanners. PURPOSE: Our first-generation prototype brain PET insert ("PETcoil") demonstrated RF-penetrability and MR-compatibility. In the second-generation PETcoil system, all analog silicon photomultiplier (SiPM) signal digitization is moved inside the detectors, which results in substantially better PET detector performance, but presents a greater technical challenge for achieving MR-compatibility. In this paper, we report results from MR-compatibility studies of two fully assembled second-generation PET insert detector modules. METHODS: We studied the effect of the presence of the two second-generation TOF-PET insert detectors on parameters that affect MR image quality and evaluated TOF-PET detector performance under different MRI pulse sequence conditions. RESULTS: With the presence of operating PET detectors, no RF noise peaks were induced in the MR images, but the relative average noise level was increased by 15%, which led to a 3.1 to 4.2-dB degradation in MR image signal-to-noise ratio (SNR). The relative homogeneity of MR images degraded by less than 1.5% with the two operating TOF-PET detectors present. The reported results also indicated that ghosting artifacts (percent signal ghosting (PSG) ⩽ 1%) and MR susceptibility artifacts (0.044 ppm) were insignificant. The PET detector data showed a relative change of less than 5% in detector module performance between running outside and within the MR bore under different MRI pulse sequences except for energy resolution in EPI sequence (13% relative difference). CONCLUSIONS: The PET detector operation did not cause any significant artifacts in MR images and the performance and time-of-flight (TOF) capability of the former were preserved under different tested MR conditions.

Complementary early-phase magnetic particle imaging and late-phase positron emission tomography reporter imaging of mesenchymal stem cells in vivo.

Stem cell-based therapies have demonstrated significant potential in clinical applications for many debilitating diseases. The ability to non-invasively and dynamically track the location and viability of stem cells post administration could provide important information on individual patient response and/or side effects. Multi-modal cell tracking provides complementary information that can offset the limitations of a single imaging modality to yield a more comprehensive picture of cell fate. In this study, mesenchymal stem cells (MSCs) were engineered to express human sodium iodide symporter (NIS), a clinically relevant positron emission tomography (PET) reporter gene, as well as labeled with superparamagnetic iron oxide nanoparticles (SPIOs) to allow for detection with magnetic particle imaging (MPI). MSCs were additionally engineered with a preclinical bioluminescence imaging (BLI) reporter gene for comparison of BLI cell viability data to both MPI and PET data over time. MSCs were implanted into the hind limbs of immunocompromised mice and imaging with MPI, BLI and PET was performed over a 30-day period. MPI showed sensitive detection that steadily declined over the 30-day period, while BLI showed initial decreases followed by later rapid increases in signal. The PET signal of MSCs was significantly higher than the background at later timepoints. Early-phase imaging (day 0-9 post MSC injections) showed correlation between MPI and BLI data (R2 = 0.671), while PET and BLI showed strong correlation for late-phase (day 10-30 post MSC injections) imaging timepoints (R2 = 0.9817). We report the first use of combined MPI and PET for cell tracking and show the complementary benefits of MPI for sensitive detection of MSCs early after implantation and PET for longer-term measurements of cell viability.

F18-FET PET in pediatric brain tumors: integrative analysis of image derived parameters and clinico-pathological data.

BACKGROUND: F18-FET PET has an established diagnostic role in adult brain gliomas. In this study we analyzed image derived static and dynamic parameters with available conventional MRI, histological, clinical and follow-up data in assessment of pediatric brain tumor patients at different stages of the disease. METHODS: Forty-four pediatric patients with median age 7 years, diagnosed with brain tumors and underwent forty-seven 18F-FET PET scans either initially (20 scans) or post-therapy (27 scans) were enrolled. Standardized analysis of summed FET PET images early from 10-20 min and late from 30-40 min post-injection were used for static (mean and maximum tumor to brain ratio [TBR] and biological tumor volume [BTV]) parameters evaluation as well as the time activity curve [TAC]. RESULTS: Nineteen out of 20 initially assessed patients had pathologically and/or clinico-radiologically proven neoplastic lesions and one patient had pathologically proven abscess. Receiver operator curve (ROC) marked early TBR max 2.95, early TBR mean 1.76, late TBR max 2.5 and late TBR mean 1.74 as discriminator points with diagnostic accuracy reaching 90% when TBR max was combined with dynamic parameters. Significant association was found between initial FET scans, early and late BTV and event free survival (EFS) (P value=0.042 and 0.005 respectively). In post-therapy assessment, the diagnostic accuracy of conventional MRI was 81.48% when used alone and 96.30% when combined with F18-FET PET scan findings. A cutoff point of 3.2 cm3 for late BTV, in post-therapy scans, was successfully marked as a predictor for therapy response (P value 0.042) and was significantly associated with EFS (P value 0.002). In FET-avid / MRI non-enhancing lesions, early TBR max was able to detect highly malignant processes (high-grade tumors in initial scans and residue/recurrence in post-therapy scans) with 80% sensitivity and 100% specificity when cutoff value of 2.25 was used (P value=0.024). In patients with FET-avid brainstem lesions, whether enhancing or non-enhancing in MRI scans, 81.8% were associated with high risk diagnoses and 68.2% of them were associated with poor therapy outcome. The degree of FET uptake matched tumor-grading, but did not show significant association with OS or EFS (P value>0.05). CONCLUSIONS: F18-FET PET seems to be an evolving pediatric neuro-imaging technique with valuable diagnostic and prognostic information at initial and post-therapy evaluation.

Modern PET-Guided Radiotherapy Planning and Treatment for Malignant Lymphoma.

Malignant lymphoma comprises a broad spectrum of diverse entities originating from different types of lymphocytes. In the last century, successive improvements of treatment possibilities have led to an continuous amelioration of patient prognosis from lethal outcome to high rates of disease control and long-term survivors. PET/CT-based imaging plays a key role in stratification of stage and treatment response. Especially for radiotherapy, an essential treatment modality for lymphoma patients, functional imaging and the reevaluation of disease activity after frontline chemotherapy has led to major improvements regarding size of treatment fields and toxicity. International expert groups like the International Lymphoma Radiation Oncology Group (ILROG) develop guidelines for the optimal use of imaging for treatment planning. The shift from uniform large-field treatment volumes to complex individual setups taking into account biological response-assessments based on functional imaging resulted in a further de-escalation of side effects and modernization of lymphoma treatment. This paper aims to summarize the use of FDG-PET-imaging for radiation therapy planning in malignant lymphoma in the context of historic and future developments, as well as associated limitations and challenges ahead. We will discuss the contemporary standard of care as recommended by international expert guidelines like the ILROG, the national comprehensive cancer network (NCCN), as well as the newly updated German S3-guidelines.

PET Imaging and Neurohistochemistry Reveal that Curcumin Attenuates Brain Hypometabolism and Hippocampal Damage Induced by Status Epilepticus in Rats.

Numerous preclinical studies provide evidence that curcumin, a polyphenolic phytochemical extracted from Curcuma longa (turmeric) has neuroprotective, anti-inflammatory and antioxidant properties against various neurological disorders. Curcumin neuroprotective effects have been reported in different animal models of epilepsy, but its potential effect attenuating brain glucose hypometabolism, considered as an early marker of epileptogenesis that occurs during the silent period following status epilepticus (SE), still has not been addressed. To this end, we used the lithium-pilocarpine rat model to induce SE. Curcumin was administered orally (300 mg/kg/day, for 17 days). Brain glucose metabolism was evaluated in vivo by 2-deoxy-2-[18F]Fluoro-D-Glucose ([18F]FDG) positron emission tomography (PET). In addition, hippocampal integrity, neurodegeneration, microglia-mediated neuroinflammation, and reactive astrogliosis were evaluated as markers of brain damage. SE resulted in brain glucose hypometabolism accompanied by body weight (BW) loss, hippocampal neuronal damage, and neuroinflammation. Curcumin did not reduce the latency time to the SE onset, nor the mortality rate associated with SE. Nevertheless, it reduced the number of seizures, and in the surviving rats, curcumin protected BW and attenuated the short-term glucose brain hypometabolism as well as the signs of neuronal damage and neuroinflammation induced by the SE. Overall, our results support the potential adaptogen-like effects of curcumin attenuating key features of SE-induced brain damage.

18F-FET-PET imaging in high-grade gliomas and brain metastases: a systematic review and meta-analysis.

PURPOSE: To provide a summary of the diagnostic performance of 18F-FET-PET in the management of patients with high-grade brain gliomas or metastases from extracranial primary malignancies. METHODS: MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews databases were searched for studies that reported on diagnostic test parameters in radiotherapy planning, response assessment, and tumour recurrence/treatment-related changes differentiation. Radiomic studies were excluded. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool and the GRADE approach. A bivariate, random-effects model was used to produce summary estimates of sensitivity and specificity. RESULTS: Twenty-six studies with a total of 1206 patients/lesions were included in the analysis. For radiotherapy planning of glioma, the pooled proportion of patients from 3 studies with 18F-FET uptake extending beyond the 20 mm margin from the gadolinium enhancement on standard MRI was 39% (95% CI, 10-73%). In 3 studies, 18F-FET-PET was also shown to be predictive of early responders to treatment, whereas MRI failed to show any prognostic value. For the differentiation of glioma recurrence from treatment-related changes, the pooled sensitivity and specificity of TBRmax 1.9-2.3 from 6 studies were 91% (95% CI, 74-97%) and 84% (95% CI, 69-93%), respectively. The respective values for brain metastases from 4 studies were 82% (95% CI, 74-88%) and 82% (95% CI, 74-88%) using TBRmax 2.15-3.11. CONCLUSION: While 18F-FET shows promise as a complementary modality to standard-of-care MRI for the management of primary and metastatic brain malignancies, further validation with standardized image interpretation methods in well-designed prospective studies are warranted.

Assessment of Cardiac Sarcoidosis: FDG PET and BMIPP SPECT.

PURPOSE OF REVIEW: Cardiac sarcoidosis (CS) is an inflammatory disease of unknown etiology that can lead to life-threatening arrhythmias, heart failure, and death. Advanced cardiac imaging modalities have improved the clinician's ability to detect this disease. The purpose of this review is to discuss the recent evidence of cardiac metabolic imaging as assessed by [18F]FDG PET and [123I]BMIPP SPECT in the evaluation of CS patients. RECENT FINDINGS: [18F]FDG PET is the gold standard to identify myocardial inflammation. [123I]BMIPP SPECT can uncover early myocardial damage as well as advanced stages of CS when fibrosis prevails. In presence of inflammation, myocardial [18F]FDG uptake is increased, but in contrast, BMIPP myocardial uptake is reduced or even suppressed. Thus, a complementary role of cardiac metabolic imaging by [18F]FDG PET and BMIPP SPECT has been proposed to detect the whole spectrum of CS. [18F]FDG PET is considered an important tool to improve the diagnosis and optimize the management of CS. The role of [123I]BMIPP SPECT in diagnosing CS is still under investigation. Further studies are needed to evaluate the clinical utility of combined cardiac metabolic imaging in the diagnosis, prognosis, and for selecting treatments in CS patients.