Magnetic Resonance Positron Emission Tomography Research Articles

An 18F-Labeled Poly(ADP-ribose) Polymerase Positron Emission Tomography Imaging Agent.

Poly(ADP-ribose) polymerase (PARP) is involved in repair of DNA breaks and is over-expressed in a wide variety of tumors, making PARP an attractive biomarker for positron emission tomography (PET) and single photon emission computed tomography imaging. Consequently, over the past decade, there has been a drive to develop nuclear imaging agents targeting PARP. Here, we report the discovery of a PET tracer that is based on the potent PARP inhibitor olaparib (1). Our lead PET tracer candidate, [18F]20, was synthesized and evaluated as a potential PARP PET radiotracer in mice bearing subcutaneous glioblastoma xenografts using ex vivo biodistribution and PET–magnetic resonance imaging techniques. Results showed that [18F]20 could be produced in a good radioactivity yield and exhibited specific PARP binding allowing visualization of tumors over-expressing PARP. [18F]20 is therefore a potential candidate radiotracer for in vivo PARP PET imaging.

PET/CT With 68Ga-PSMA in Prostate Cancer: Radiopharmaceutical Background and Clinical Implications

In the last twenty years, positron emission tomography / computed tomography (PET/CT) with radiolabeled choline, represented the most powerful imaging modality for prostate cancer (PCa). However, the low positive detection rate of the technique for PSA < 1 ng/ml prompted the development of other tracers for imaging PCa. We performed a critical review of 68Ga-PSMA, a receptor ligand tracer, which has been identified as the most promising radiopharmaceutical for imaging PCa. The most promising feature of this radiopharmaceutical is the high positive detection rate for prostate specific antigen (PSA) levels < 1 ng/ml or less (i.e., PSA < 0.5 ng/ml). 68Ga-PSMA detection rate is also sensitive to PSA kinetics, expressed either as PSA doubling time or PSA velocity. There are initial results indicating that 68Ga-PSMA may significantly affect the clinical management of PCa patients, even though the additional advantages in comparison to radiolabeled choline need to be further supported in future perspective studies. Other clinical implications, such as whether 68Ga-PSMA PET/CT predicts PCa-specific survival, have not yet been investigated. Numerous clinical studies have been published, some of them with histopathological verification so that despite the recent introduction in the clinical field reliable estimation of sensitivity and specificity of 68Ga-PSMA PET/CT have been obtained through meta-analyses. Most clinical studies with PET/CT with 68Ga-PSMA are retrospective, single-institutional studies and in many cases include heterogeneous patient cohorts. Thus, multidisciplinary, well-throughout prospective trials are needed to better define the clinical implications of 68Ga- PSMA PET/CT in PCa patients. The increasing availability of positron emission tomography / magnetic resonance (PET/MR) hybrid devices promotes the use of this radiopharmaceutical especially at initial staging when identification of tumor localization and of extra-prostatic disease represent clinically relevant questions. PSMA cold ligands can also be labeled with beta emitters with good chemical stability so that 68Ga-PSMA PET/CT can be used to guide radiometabolic therapy of advanced metastatic PCa patients through 177Lu-labeled PSMA ligands. PSMA labeled ligands appear very promising for diagnosis and treatment of PCa.

Biological imaging for individualized therapy in radiation oncology: part I physical and technical aspects.

Recently, there has been an increase in the imaging modalities available for radiotherapy planning and radiotherapy prognostic outcome: dual energy computed tomography (CT), dynamic contrast enhanced CT, dynamic contrast enhanced magnetic resonance imaging (MRI), diffusion-weighted MRI, positron emission tomography-CT, dynamic contrast enhanced ultrasound, MR spectroscopy and positron emission tomography-MR. These techniques enable more precise gross tumor volume definition than CT alone and moreover allow subvolumes within the gross tumor volume to be defined which may be given a boost dose or an individual voxelized dose prescription may be derived. With increased plan complexity care must be taken to immobilize the patient in an accurate and reproducible manner. Moreover the physical and technical limitations of the entire treatment planning chain need to be well characterized and understood, interdisciplinary collaboration ameliorated (physicians and physicists within nuclear medicine, radiology and radiotherapy) and image protocols standardized.

Validation of LYSO Scintillators Coupled to SensL C-Series SiPM's Detectors

Simulation and experimental procedures, using Na-22 sources, were carried out in order to examine the spatial resolution of a preclinical positron emission tomographymagnetic resonance imaging (PETMRI) system, due to the innovative use of Silicon Photomultiplier (SiPM) detectors coupled with doubled jaw layer lutetium yttrium oxyorthosilicate (LYSO) crystals. Optical properties of LYSO scintillation crystals were examined, and the optimal crystal configuration was determined. Noise-equivalent count rate curves were analyzed in order to determine the stability of the PET system. The highest resolution in the 511-keV photopeak was measured as 10.84 for 27.5 V, and in the 1274-keV photopeak, the best resolution was recorded as 12.75 again for 27.5 V. Moreover, simulation and experimental images of the SiPM, for 1.2-mm and 1.68-mm pixel pitch size, were compared, showing that for 27.5 V of bias voltage, the spatial resolution is better, while the gain and the noise is low. However, for 29V, the gain is better, but there is more noise.

18F]FDG PET/MR enterography for the assessment of inflammatory activity in Crohn's disease: comparison of different MRI and PET parameters.

To evaluate the diagnostic performance of integrated whole-body positron emission tomography (PET)/magnetic resonance (MR) enterography in patients with Crohn's disease (CD). Fifty patients with known CD and recurrent symptoms underwent ileocolonoscopy (reference standard) as well as PET/MR enterography. Seven ileocolonic segments were endoscopically analysed using the Simplified Endoscopic Activity Score for Crohn's Disease (SES-CD) and additionally classified into three categories of inflammation (none, mild to moderate and severe ulcerative inflammation). A total of 14 PET/MR parameters were applied for the assessment of inflamed segments. Contingency tables and the chi-squared test were used for the analysis of qualitative parameters, and the Mann-Whitney U test and receiver operating characteristic (ROC) curve for the analysis of quantitative parameters. The PET/MR parameters were ranked according to their diagnostic value by random forest classification. Correlations between PET/MR parameters and the severity of inflammation on endoscopy and SES-CD were tested using Spearman's rank correlation test. A total of 309 segments could be analysed. Based on multivariate regression analysis, wall thickness and the comb sign were the most importantparameters for predicting segments with active inflammation of any type. SUVmax ratio of the bowel segment (relative to SUVmax of the liver) was the most important parameter for detecting segments with severeulcerative inflammation. Wall thickness was the only parameter that moderately correlated with inflammation severity on endoscopy as well as with SES-CD (ρ = 0.56 and 0.589, both p< 0.001). PET/MR enterography is an excellent noninvasive diagnostic method, and both MR parameters and PET findings provided high accuracy in detecting inflamed segments.

MR-based motion correction for cardiac PET parametric imaging: a simulation study

BackgroundBoth cardiac and respiratory motions bias the kinetic parameters measured by dynamic PET. The aim of this study was to perform a realistic positron emission tomography-magnetic resonance (PET-MR) simulation study using 4D XCAT to evaluate the impact of MR-based motion correction on the estimation of PET myocardial kinetic parameters using PET-MR. Dynamic activity distributions were obtained based on a one-tissue compartment model with realistic kinetic parameters and an arterial input function. Realistic proton density/T1/T2 values were also defined for the MRI simulation. Two types of motion patterns, cardiac motion only (CM) and both cardiac and respiratory motions (CRM), were generated. PET sinograms were obtained by the projection of the activity distributions. PET image for each time frame was obtained using static (ST), gated (GA), non-motion-corrected (NMC), and motion-corrected (MC) methods. Voxel-wise unweighted least squares fitting of the dynamic PET data was then performed to obtain K1 values for each study. For each study, the mean and standard deviation of K1 values were computed for four regions of interest in the myocardium across 25 noise realizations.ResultsBoth cardiac and respiratory motions introduce blurring in the PET parametric images if the motion is not corrected. Conventional cardiac gating is limited by high noise level on parametric images. Dual cardiac and respiratory gating further increases the noise level. In contrast to GA, the MR-based MC method reduces motion blurring in parametric images without increasing noise level. It also improves the myocardial defect delineation as compared to NMC method. Finally, the MR-based MC method yields lower bias and variance in K1 values than NMC and GA, respectively. The reductions of K1 bias by MR-based MC are 7.7, 5.1, 15.7, and 29.9% in four selected 0.18-mL myocardial regions of interest, respectively, as compared to NMC for CRM. MR-based MC yields 85.9, 75.3, 71.8, and 95.2% less K1 standard deviation in the four regions, respectively, as compared to GA for CRM.ConclusionsThis simulation study suggests that the MR-based motion-correction method using PET-MR greatly reduces motion blurring on parametric images and yields less K1 bias without increasing noise level.

Quantitative PET-MRI for early treatment response assessment in pancreatic ductal adenocarcinoma.

520 Background: There is an unmet need for improved non-invasive markers to assess early treatment response in pancreatic ductal adenocarcinoma (PDAC). Assessing early treatment response using tumor size on anatomic imaging or serum carbohydrate antigen 19-9 (CA19-9) level is unreliable. In contrast, metabolic and functional imaging is a promising new tool that may differentiate responders from non-responders early on during therapy. Therefore, the objective of this pilot study was to explore the potential of integrated positron emission tomography-magnetic resonance imaging (PET-MRI) to provide imaging biomarkers of early (4 weeks post treatment initiation) response in patients with advanced PDAC. Methods: 13 patients with biopsy-proven locally advanced or metastatic PDAC underwent integrated 18F-fluorodeoxyglucose PET-MRI through the abdomen prior to, and again at 4 weeks post, treatment initiation. Patients also had computed tomography (CT) imaging of the chest, abdomen, and pelvis and serum CA19-9 levels measured, as per standard of care. Patients were classified as responders or non-responders according to RECIST (Response Evaluation Criteria In Solid Tumors) on delayed CT, at 8-12 weeks interval post treatment initiation. Changes in metabolic tumor volume (MTV) and total lesion glycolysis (TLG) from PET, and apparent diffusion coefficient (ADC) from diffusion-weighted MRI at 4 weeks were compared between responders and non-responders. Results: Of the 13 patients, there were 7 responders (partial response by RECIST) and 6 non-responders (progressive or stable disease by RECIST). After 4 weeks of therapy, responders had a significantly greater decrease in MTV (p = 0.003) and TLG (p = 0.006) compared to non-responders. Responders also had a significantly greater increase in mean and minimum ADC (p = 0.004 and p = 0.024, respectively) compared to non-responders. Change in tumor size at 4 weeks was not significantly different between responders and non-responders (p = 0.11). Conclusions: Integrated PET-MRI can provide early assessment of treatment response in patients with advanced PDAC.

Positron emission tomography-magnetic resonance imaging (PET-MRI) for response assessment after radiation therapy of cervical carcinoma: a pilot study

BackgroundAdvanced stage cervical cancer is primarily treated by radiotherapy. Local tumor control is a prerequisite for cure. Imaging after treatment is controversial. Positron emission tomography (PET) combined with computer tomography (PET-CT) shows great promise for detecting metastases. On the other hand, magnetic resonance imaging (MRI) is superior in depicting anatomical details. The combination of PET-MRI could result in more accurate evaluation of cervical cancer treatment outcome. The aim of this pilot study is to share our initial experience with PET-MRI in the evaluation of treatment response in cervical cancer after radiation treatment.MethodsTen patients with cervical carcinoma (FIGO ≥IB2) were prospectively evaluated. Eleven weeks (median; range 8–15 weeks) after radiation therapy, treatment response was evaluated by PET-MRI. The PET, MRI, and combined PET-MRI images were evaluated for the presence of local residual tumor and metastasis. Diagnostic performance was assessed by area under the receiver operator characteristic (ROC) curve for evaluation of local residual tumor. The readers were blinded for outcome data. Local residual disease, metastasis, diagnostic confidence, and change of opinion were scored on a 5-point Likert scale. The reference standard consisted of pathology and/or follow-up according to the clinical guidelines.ResultsThree out of ten patients had local residual abnormalities suggestive for tumor residue after radiation treatment. The availability of both PET and MRI resulted in an increase in diagnostic confidence in 80–90% of all patients. Change of opinion was observed in 70% and change of policy in 50%, especially in the group with residual tumor. The diagnostic accuracy increased significantly for the radiologist if PET-MRI was combined (AUC .54 versus .83).ConclusionsPET-MRI shows promise for evaluation of treatment response after radiation for cervical cancer, especially increasing diagnostic confidence, while potentially increasing diagnostic performance.

PET/MR Imaging of Malondialdehyde-Acetaldehyde Epitopes With a Human Antibody Detects Clinically Relevant Atherothrombosis

BackgroundOxidation-specific epitopes (OSEs) are proinflammatory, and elevated levels in plasma predict cardiovascular events. ObjectivesThe purpose of this study was to develop novel positron emission tomography (PET) probes to noninvasively image OSE-rich lesions. MethodsAn antigen-binding fragment (Fab) antibody library was constructed from human fetal cord blood. After multiple rounds of screening against malondialdehyde-acetaldehyde (MAA) epitopes, the Fab LA25 containing minimal nontemplated insertions in the CDR3 region was identified and characterized. In mice, pharmacokinetics, biodistribution, and plaque specificity studies were performed with Zirconium-89 (89Zr)-labeled LA25. In rabbits, 89Zr-LA25 was used in combination with an integrated clinical PET/magnetic resonance (MR) system. 18F-fluorodeoxyglucose PET and dynamic contrast-enhanced MR imaging were used to evaluate vessel wall inflammation and plaque neovascularization, respectively. Extensive ex vivo validation was carried out through a combination of gamma counting, near infrared fluorescence, autoradiography, immunohistochemistry, and immunofluorescence. ResultsLA25 bound specifically to MAA epitopes in advanced and ruptured human atherosclerotic plaques with accompanying thrombi and in debris from distal protection devices. PET/MR imaging 24 h after injection of 89Zr-LA25 showed increased uptake in the abdominal aorta of atherosclerotic rabbits compared with nonatherosclerotic control rabbits, confirmed by ex vivo gamma counting and autoradiography. 18F-fluorodeoxyglucose PET, dynamic contrast-enhanced MR imaging, and near-infrared fluorescence signals were also significantly higher in atherosclerotic rabbit aortas compared with control aortas. Enhanced liver uptake was also noted in atherosclerotic animals, confirmed by the presence of MAA epitopes by immunostaining. Conclusions89Zr-LA25 is a novel PET radiotracer that may allow noninvasive phenotyping of high-risk OSE-rich lesions.

Nuclear Medicine in India: A Historical Journey.

Evidence-based historical accounts of critical events, which shaped nuclear medicine in India today, are presented in this article. There was parallel activity happening in the northern and western region of India in the early 60s. Radiation Medicine Center (RMC) at Mumbai inaugurated in September 1963 by Dr. Bhabha; and Institute of Nuclear Medicine and Allied Sciences, Delhi dedicated to the nation in February 1964. The isotope division of Bhabha Atomic Research Center endured as the backbone in the supply of indigenously produced medical radioisotopes in research reactors APSARA (1958) and CIRUS (1960). Design and dispatch of economical generators (loaded with low specific activity 99Mo) with indigenously designed solvent extraction (Methyl Ethyl Ketone) technique had led to rapid growth of nuclear medicine facilities in the country. As per recently released list (July 2018) of the Atomic Energy Regulatory Board, there are 293 nuclear medicine departments in the country. Of which 14% are in the government sector, and the remaining 86% are under private ownership. There are currently 233 functioning gamma cameras (Single-photon emission computed tomography [SPECT]/SPECT–computed tomography [CT]) units in India since 1969 when the first gamma camera was commissioned at RMC. The first medical cyclotron (2002) and first positron emission tomography (PET) (2002) and first PET-CT (2004) in Mumbai had triggered revolution of molecular imaging in India. There are 222 PET-CT, 3 PET-magnetic resonance imaging scanners, and 19 cyclotrons operating currently. India has witnessed relatively slower headways in terms of high dose radionuclide therapy facilities. After first indoor facility at RMC in 1964, only 92 radionuclide therapy (isolation) wards have come up with no more than 200 beds for the entire country in the last 54 years. India started Delhi university approved structured postgraduate diploma in nuclear medicine in 1963 at the Institute of Nuclear Medicine and Allied Sciences (INMAS), first of its kind course in the world at that time. RMC started Mumbai University recognized diploma courses for physicians (Diploma in Radiation Medicine) and technologists (Diploma in Medical Radioisotope Techniques) in 1973. National Board of Examination (Government of India) recognized nuclear medicine as a broad specialty in 1982 and accredited RMC for training for Diplomate of National Board. Doctor of Medicine (MD) started first time in India and Asia at Sanjay Gandhi Postgraduate Institute, Lucknow in 1990. Doctorate of Therapeutic Nuclear Medicine commenced at All India Institute of Medical Sciences Delhi in 2015. There are 18 teaching hospitals currently imparting MD/DNB nuclear medicine residency for physicians with annual intake of 50. Eighteen institutions are offering bachelors and masters programs for nuclear medicine technology with an average annual intake of 110–120 students. Society of Nuclear Medicine, India (SNMI) is the oldest and largest professional body with total life membership of 1425 nuclear medicine professionals. SNMI was established in 1967 and hosted the first Annual Conference at RMC, Mumbai in 1968. Since then, SNMI is organizing its Annual Conferences in various parts of the country with the objective of scientific exchange and popularizing the modality amongst clinicians. Postgraduate Institute of Medical Education Research is hosting the 50th Annual Conference of SNMI (SNMICON-18) as mark of golden jubilee celebration.

Low cortical iron and high entorhinal cortex volume promote cognitive functioning in the oldest-old

The aging brain is characterized by an increased presence of neurodegenerative and vascular pathologies. However, there is substantial variation regarding the relationship between an individual's pathological burden and resulting cognitive impairment. To identify correlates of preserved cognitive functioning at highest age, the relationship between β-amyloid plaque load, presence of small vessel cerebrovascular disease (SVCD), iron-burden, and brain atrophy was investigated. Eighty cognitively unimpaired participants (44 oldest-old, aged 85–96 years; 36 younger-old, aged 55–80 years) were scanned by integrated positron emission tomography–magnetic resonance imaging for assessing beta regional amyloid plaque load (18F-flutemetamol), white matter hyperintensities as an indicator of SVCD (fluid-attenuated inversion recovery–magnetic resonance imaging), and iron load (quantitative susceptibility mapping). For the oldest-old group, lower cortical volume, increased β-amyloid plaque load, prevalence of SVCD, and lower cognitive performance in the normal range were found. However, compared to normal-old, cortical iron burden was lower in the oldest-old. Moreover, only in the oldest-old, entorhinal cortex volume positively correlated with β-amyloid plaque load. Our data thus indicate that the co-occurrence of aging-associated neuropathologies with reduced quantitative susceptibility mapping measures of cortical iron load constitutes a lower vulnerability to cognitive loss.

Superiority of 68Ga-DOTATATE over 18F-FDG and anatomic imaging in the detection of succinate dehydrogenase mutation (SDHx )-related pheochromocytoma and paraganglioma in the pediatric population.

To evaluate and compare diagnostic performance of 68Ga-DOTA(0)-Tyr(3)-octreotate (68Ga-DOTATATE) with 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography-computed tomography (PET/CT) and anatomic imaging using computed tomography and/or magnetic resonance (CT/MR) imaging in detection of SDHx-related pheochromocytomas and paragangliomas (PPGLs) in pediatric patients. Nine pediatric patients (5:4, girls:boys; 14.6 ± 2.0years) with an SDHx-related mutation (SDHB:SDHA:SDHD, n = 7:1:1) were included in this retrospective study. At the time of initial diagnosis, 7/9 patients had metastatic disease. They underwent CT/MR imaging along with PET/CT using 68Ga-DOTATATE (n = 9), 18F-FDG (n = 8), and positron emission tomography-magnetic resonance imaging (PET/MR) using 18F-FDG (n = 1). In this manuscript, 18F-FDG PET/CT refers to both 18F-FDG PET/CT and 18F-FDG PET/MR. The per-lesion, per-region, and per-patient detection rates were compared and calculated for each of the imaging modalities. A composite of all functional and anatomic imaging studies served as the imaging comparator. Eight out of nine patients were positive for PPGLs on the imaging studies that demonstrated 107 lesions in 22 anatomic regions on the imaging comparator. The per-lesion detection rates for 68Ga-DOTATATE PET/CT, 18F-FDG PET/CT, and CT/MR imaging were 93.5% (95%CI, 87.0% to 97.3%); 79.4% (95%CI, 70.5% to 86.6%); and 73.8% (95%CI, 64.5% to 81.9%), respectively. The per-lesion detection rate for 68Ga-DOTATATE PET/CT was significantly higher than that of 18F-FDG PET/CT (p = 0.001) or CT/MR imaging (p < 0.001). In all of the anatomic regions except abdomen, the per-lesion detection rates for 68Ga-DOTATATE PET/CT was found to be equal or superior to 18F-FDG PET/CT, and CT/MR imaging. The per-region detection rate was 100% (95%CI, 84.6% to 100%) for 68Ga-DOTATATE PET/CT and 90.9% (95%CI, 70.8% to 98.9%) for both 18F-FDG PET/CT and CT/MR imaging. The per-patient detection rates for 68Ga-DOTATATE PET/CT, 18FDG PET/CT, and CT/MR imaging were all 100% (95%CI, 63.1% to 100%). Our preliminary study demonstrates the superiority of 68Ga-DOTATATE PET/CT in localization of SDHx-related PPGLs in pediatric population compared to 18F-FDG PET/CT and CT/MR imaging with the exception of abdominal (excluding adrenal and liver) lesions, and suggests that it might be considered as a first-line imaging modality in pediatric patients with SDHx-related PPGLs.

PET/MR Tomographs: A Review with Technical, Radiochemical and Clinical Perspectives.

In the last decade, an increasing number of positron emission tomography / magnetic resonance (PET/MR) tomographs were installed and many clinical studies were performed in the neurological field. Although PET/MR has many favorable properties to support the application in brain imaging, attenuation correction, and therefore accurate quantification, is a problem that still requires optimal solution. In this review we have summarized the three main methods that are currently used to correct attenuation in PET/MR, namely atlas- or template-based methods, segmentation-based methods, and reconstruction-based methods. There is currently active ongoing research to refine available methods and improvements are reasonably expected in the next years. Clinical studies using PET/MR focused mainly on neurodegenerative and neurooncological disorders. PET/MR hybrids tomographs provided promising scientific results and were logistically more convenient for patients. Additionally, in order to explore all potential clinical benefits of this hybrid technology, the design and development of multimodal contrast agents has constantly increased the attention of radiochemists. Many PET/MR dual probes have been already devised, particularly in the nanotechnology field, sometimes preceding the identification of a clear diagnostic application in medicine. In the near future, we predict more clinical studies as the availability of PET/MR will further increase and new tracers for neurodegenerative disorders will accept broader clinical acceptance.

Noninfectious aortitis: what the cardiologist needs to know.

To sum up a group of noninfectious inflammatory diseases of the aorta and its branches relevant to a cardiologist's daily routine. To describe pathogenetic and clinical advances as well as modern diagnostic tools. To overview most recent treatment options and patient-tailored therapies. To provide an insight in future directions of research. Pathophysiology of large vessel vasculitides (LVV) are still poorly defined. At least a certain number of patients with idiopathic periaortitis seem to part of the group of IgG4-related diseases which has implications for therapy. Modern diagnostic modalities as Positron-Emission-Tomography (PET)-computed tomography and PET-magnetic resonance tomography proof to be helpful to diagnose or excluded LVV and emerge as long-term surveillance tool. Biological therapy yields varying results but is reported to be important for patients nonresponding or relapsing under glucocorticoid therapy. Owing to the multifactorial pathogenesis and the small number of cases of LVV further interdisciplinary efforts are necessary to elucidate the pathogenesis of this group of diseases. Technical progress in radiology and nuclear medicine supports clinical, histological, and laboratory findings to increase diagnostic precision. There are several therapies emerging that may have the potential to support patient-tailored treatment approaches in glucocorticoid refractory or relapsing disease.

Molecular Imaging of Cardiac Metabolism, Innervation, and Conduction

Cardiac diseases have complex molecular origins. However, current clinical diagnostic tools are often inadequate to uncover specific molecular components of cardiac pathologies. Thus, we are still lacking a detailed understanding of disease progression, and both patient diagnosis and treatment are often inaccurate. Molecular imaging could play a leading role in translating basic research to both preclinical and clinical cardiac research, ultimately improving our understanding and management of human disease. In this review, we highlight the diversity of current molecular imaging tools that have been used in clinical research or have reached the stage of clinical translation. Facilitated by the steadily increasing infrastructure of clinical positron emission tomography and positron emission tomography-magnetic resonance imaging cameras and advancing gating analysis, these tools allow the implementation of clinical cardiac molecular imaging trials to deepen our knowledge of human disease and improve patient care.

Novel bandlike signal abnormality suggestive of heterotopia in patient with a KCNQ1 frameshift mutation.

SummaryMalformations of cortical development are associated with epilepsy and cognitive dysfunction, and can occur in patients with SCN1A ion channel mutations. We report a novel and subtle bandlike subcortical heterotopia on integrated positron emission tomography–magnetic resonance imaging ( PET‐MRI) in a patient with treatment‐resistant epilepsy due to a de novo KCNQ1 frameshift mutation. Our case highlights the potential for other channel mutations to cause both epilepsy and cortical malformations. Further scrutiny of high contrast resolution MRI studies is warranted for patients with KCNQ1 and other epilepsy genes to further define their extended phenotype.

Brain PET and functional MRI: why simultaneously using hybrid PET/MR systems?

In the last 20 years growing attention has been devoted to multimodal imaging. The recent literature is rich of clinical and research studies that have been performed using different imaging modalities on both separate and integrated positron emission tomography (PET) and magnetic resonance (MR) scanners. However, today, hybrid PET/MR systems measure signals related to brain structure, metabolism, neurochemistry, perfusion, and neuronal activity simultaneously, i.e. in the same physiological conditions. A frequently raised question at meeting and symposia is: "Do we really need a hybrid PET/MR system? Are there any advantages over acquiring sequential and separate PET and MR scans?" The present paper is an attempt to answer these questions specifically in relation to PET combined with functional magnetic resonance imaging (fMRI) and arterial spin labeling. We searched (last update: June 2017) the databases PubMed, PMC, Google Scholar and Medline. We also included additional studies if they were cited in the selected articles. No language restriction was applied to the search, but the reviewed articles were all in English. Among all the retrieved articles, we selected only those performed using a hybrid PET/MR system. We found a total of 17 papers that were selected and discussed in three main groups according to the main radiopharmaceutical used: 18F-fluorodeoxyglucose (18F-FDG) (N.=8), 15O-water (15O-H2O) (N.=3) and neuroreceptors (N.=6). Concerning studies using 18F-FDG, simultaneous PET/fMRI revealed that global aspects of functional organization (e.g. graph properties of functional connections) are partially associated with energy consumption. There are remarkable spatial and functional similarities across modalities, but also discrepant findings. More work is needed on this point. There are only a handful of papers comparing blood flow measurements with PET 15O-H2O and MR arterial spin label (ASL) measures, and they show significant regional CBF differences between these two modalities. However, at least in one study the correlation at the level of gray, white matter, and whole brain is rather good (r=0.94, 0.8, 0.81 respectively). Finally, receptor studies show that simultaneous PET/fMRI could be a useful tool to characterize functional connectivity along with dynamic neuroreceptor adaptation in several physiological (e.g. working memory) or pathological (e.g. pain) conditions, with or without drug administrations. The simultaneous acquisition of PET (using a number of radiotracers) and functional MRI (using a number of sequences) offers exciting opportunities that we are just beginning to explore. The results thus far are promising in the evaluation of cerebral metabolism/flow, neuroreceptor adaptation, and network's energetic demand.

Early Clinical Experiences with Positron Emission Tomography–Magnetic Resonance Imaging in Epilepsy: Implications for Modeling the Neurovascular Unit

AbstractCortical function in normal and pathologic neurologic states is largely influenced by the activity of the neurovascular unit. Hybrid technologies that combine positron emission tomography and magnetic resonance imaging (PET/MRI) offer a chance for simultaneous noninvasive evaluation of cortical glucose consumption, blood flow, and cerebrovascular reactivity. We present differing PET/MRI results for two pediatric patients undergoing evaluation for medically refractory seizures, interpreted in the context of neurovascular unit behavior, suggesting the presence of ultrastructural changes at the level of the blood brain barrier in various epilepsy disorders.

How to Provide Gadolinium-Free PET/MR Cancer Staging of Children and Young Adults in Less than 1h: the Stanford Approach.

To provide clinically useful gadolinium-free whole-body cancer staging of children and young adults with integrated positron emission tomography/magnetic resonance (PET/MR) imaging in less than 1h. In this prospective clinical trial, 20 children and young adults (11-30 years old, 6 male, 14 female) with solid tumors underwent 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET/MR on a 3T PET/MR scanner after intravenous injection of ferumoxytol (5mg Fe/kg) and [18F]FDG (2-3MBq/kg). Time needed for patient preparation, PET/MR image acquisition, and data processing was compared before (n=5) and after (n=15) time-saving interventions, using a Wilcoxon test. The ferumoxytol-enhanced PET/MR images were compared with clinical standard staging tests regarding radiation exposure and tumor staging results, using Fisher's exact tests. Tailored workflows significantly reduced scan times from 36 to 24min for head to mid thigh scans (p<0.001). These streamlined PET/MR scans were obtained with significantly reduced radiation exposure (mean 3.4mSv) compared to PET/CT with diagnostic CT (mean 13.1mSv; p=0.003). Using the iron supplement ferumoxytol "off label" as an MR contrast agent avoided gadolinium chelate administration. The ferumoxytol-enhanced PET/MR scans provided equal or superior tumor staging results compared to clinical standard tests in 17 out of 20 patients. Compared to PET/CT, PET/MR had comparable detection rates for pulmonary nodules with diameters of equal or greater than 5mm (94 vs. 100%), yet detected significantly fewer nodules with diameters of less than 5 mm (20 vs 100%) (p=0.03). [18F]FDG-avid nodules were detected with slightly higher sensitivity on the PET of the PET/MR compared to the PET of the PET/CT (59 vs 49%). Our streamlined ferumoxytol-enhanced PET/MR protocol provided cancer staging of children and young adults in less than 1h with equivalent or superior clinical information compared to clinical standard staging tests. The detection of small pulmonary nodules with PET/MR needs to be improved.

Multiparametric [11C]Acetate positron emission tomography-magnetic resonance imaging in the assessment and staging of prostate cancer

BackgroundThe aim of this study was to evaluate whether MP [11C]Acetate PET-MRI enables an accurate differentiation of benign and malignant prostate tumors as well as local and distant staging.Materials and methodsFifty-six consecutive patients fulfilling the following criteria were included in this IRB-approved prospective study: elevated PSA levels or suspicious findings at digital rectal examination or TRUS; and histopathological verification. All patients underwent MP [11C]Acetate PET-MRI of the prostate performed on separate scanners with PET/CT using [11C]Acetate and 3T MP MR imaging. Appropriate statistical tests were used to determine diagnostic accuracy, local and distant staging.ResultsMP imaging with two MRI parameters (T2w and DWI) achieved the highest sensitivity, specificity, and diagnostic accuracy of 95%, 68.8%, and 88%, with an AUC of 0.82 for primary PCa detection. Neither assessments with a single parameter (AUC, 0.54–0.79), nor different combinations with up to five parameters (AUC, 0.67–0.79) achieved equally good results. MP [11C]Acetate PET-MRI improved local staging with a sensitivity, specificity, and diagnostic accuracy of 100%, 96%, and 97% compared to MRI alone with 72.2%, 100%, and 95.5%. MP [11C]Acetate PET-MRI correctly detected osseous and liver metastases in five patients.ConclusionsMP [11C]Acetate PET-MRI merges morphologic with functional information, and allows insights into tumor biology. MP [11C]Acetate PET-MRI with two MRI-derived parameters (T2 and DWI) yields the highest diagnostic accuracy. The addition of more parameters does not improve diagnostic accuracy of primary PCa detection. MP [11C]Acetate PET-MRI facilitates improved local and distant staging, providing “one-stop” staging in patients with primary PCa, and therefore has the potential to improve therapy.Patient summaryIn this report we investigated MP [11C]Acetate PET-MRI for detection, local and distant staging of prostate cancer. We demonstrate that MP [11C]Acetate PET-MRI with two MRI-derived parameters (T2 and DWI) achieves the best diagnostic accuracy for primary prostate cancer detection and that MP [11C]Acetate PET-MRI enables an improved local and distant staging.