Real-time motion-enabling positron emission tomography of the brain of upright ambulatory humans.

BACKGROUND: Mobile upright PET devices have the potential to enable previously impossible neuroimaging studies. Currently available options are imagers with deep brain coverage that severely limit head/body movements or imagers with upright/motion enabling properties that are limited to only covering the brain surface. METHODS: In this study, we test the feasibility of an upright, motion-compatible brain imager, our Ambulatory Motion-enabling Positron Emission Tomography (AMPET) helmet prototype, for use as a neuroscience tool by replicating a variant of a published PET/fMRI study of the neurocorrelates of human walking. We validate our AMPET prototype by conducting a walking movement paradigm to determine motion tolerance and assess for appropriate task related activity in motor-related brain regions. Human participants (n = 11 patients) performed a walking-in-place task with simultaneous AMPET imaging, receiving a bolus delivery of F18-Fluorodeoxyglucose. RESULTS: Here we validate three pre-determined measure criteria, including brain alignment motion artifact of less than <2 mm and functional neuroimaging outcomes consistent with existing walking movement literature. CONCLUSIONS: The study extends the potential and utility for use of mobile, upright, and motion-tolerant neuroimaging devices in real-world, ecologically-valid paradigms. Our approach accounts for the real-world logistics of an actual human participant study and can be used to inform experimental physicists, engineers and imaging instrumentation developers undertaking similar future studies. The technical advances described herein help set new priorities for facilitating future neuroimaging devices and research of the human brain in health and disease.

Brain imaging plays an important role in understanding how the human brain functions in both health and disease. However, traditional brain scanners often require people to remain still, limiting the study of the brain in motion, and excluding people who cannot remain still. To overcome this, our team developed an imager that moves with a person's head, which uses a suspended ring of lightweight detectors that fit to the head. Using our imager, we were able to obtain clear brain images of people walking in place that showed the expected brain activity patterns during walking. Further development of our imager could enable it to be used to better understand real-world brain function and behavior, enabling enhanced knowledge and treatment of neurological conditions.

More Similar than Different: Memory, Executive Functions, Cortical Thickness, and Glucose Metabolism in Biomarker-Positive Alzheimer's Disease and Behavioral Variant Frontotemporal Dementia.

Background: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are typically associated with very different clinical and neuroanatomical presentations; however, there is increasing recognition of similarities. Objective: To examine memory and executive functions, as well as cortical thickness, and glucose metabolism in AD and bvFTD signature brain regions. Methods: We compared differences in a group of biomarker-defined participants with Alzheimer's disease and a group of clinically diagnosed participants with bvFTD. These groups were also contrasted with healthy controls (HC). Results: As expected, memory functions were generally more impaired in AD, followed by bvFTD, and both clinical groups performed more poorly than the HC group. Executive function measures were similar in AD compared to bvFTD for motor sequencing and go/no-go, but bvFTD had more difficulty with a set shifting task. Participants with AD showed thinner cortex and lower glucose metabolism in the angular gyrus compared to bvFTD. Participants with bvFTD had thinner cortex in the insula and temporal pole relative to AD and healthy controls, but otherwise the two clinical groups were similar for other frontal and temporal signature regions. Conclusions: Overall, the results of this study highlight more similarities than differences between AD and bvFTD in terms of cognitive functions, cortical thickness, and glucose metabolism. Further research is needed to better understand the mechanisms mediating this overlap and how these relationships evolve longitudinally.

18 F-fludeoxyglucose positron emission computed tomography (18 F-FDG-PET/CT) versus 68 Ga-DOTATATE-PET/CT in patients with head and neck cancer: Comparisons and implications for treatment.

BACKGROUND: Tumor-specific molecular imaging in head and neck squamous cell carcinoma (HNSCC) is not well established. Somatostatin receptors (SSTRs) are found in solid tumors, including HNSCC. 68 Ga-DOTATATE, a commercially available radionuclide that binds SSTRs, may have utility in imaging HNSCC. METHODS: Patients with HNSCC received pretreatment imaging with 18 F-FDG-PET/CT and 68 Ga-DOTATATE. Imaging was compared for concordance. When available, surgical resection specimens were compared to pretreatment imaging findings. Historic HNSCC tumor specimens were assessed for both SSTR and p16/human papilloma virus (HPV) expression. RESULTS: Twenty patients were imaged. Fifteen had oropharyngeal cancer. Primary tumor site was concordant between imaging modalities for all patients. One of 45 lymph nodes was discordant. Retrospective specimen review showed a significant correlation with SSTR expression and HPV/p16 expression. No adverse events occurred. CONCLUSIONS: 68 Ga-DOTATATE imaging is safe and effective in HNSCC. SSTR expression may be increased in HPV-mediated tumors. Targeted therapies to SSTR should be explored.

Quantitative single photon emission computed tomography derived standardized uptake values on 99mTc-PYP scan in patients with suspected ATTR cardiac amyloidosis.

Technetium-99 pyrophosphate scintigraphy (99mTc-PYP) provides qualitative and semiquantitative diagnosis of ATTR cardiac amyloidosis (ATTR-CA) using the Perugini scoring system and heart/contralateral heart ratio (H/CL) on planar imaging. Standardized uptake values (SUV) with quantitative single photon emission computed tomography (xSPECT/CT) can offer superior diagnostic accuracy and quantification through precise myocardial contouring that enhances assessment of ATTR-CA burden. We examined the correlation of xSPECT/CT SUVs with Perugini score and H/CL ratio. We also assessed SUV correlation with cardiac magnetic resonance (CMR), echocardiographic, and baseline clinical characteristics. Retrospective review of 78 patients with suspected ATTR-CA that underwent 99mTc-PYP scintigraphy with xSPECT/CT. Patients were grouped off Perugini score (Grade 0-1 and Grade 2-3), H/CL ratio (≥ 1.5 and < 1.5). Two cohorts were also created: myocardium SUVmax > 1.88 and ≤ 1.88 at 1-hour based off an AUC curve with 1.88 showing the greatest sensitivity and specificity. Cardiac SUV retention index was calculated as [SUVmax myocardium/SUVmax vertebrae] × SUVmax paraspinal muscle. Primary outcome was myocardium SUVmax at 1-hour correlation with Perugini grades, H/CL ratio, CMR, and echocardiographic data. Higher Perugini Grades corresponded with higher myocardium SUVmax values, especially when comparing Perugini Grade 3 to Grade 2 and 1 (3.03 ± 2.1 vs 0.59 ± 0.97 and 0.09 ± 0.2, P < 0.001). Additionally, patients with H/CL ≥ 1.5 had significantly higher myocardium SUVmax compared to patients with H/CL ≤ 1.5 (2.92 ± 2.18 vs 0.35 ± 0.60, P < 0.01). Myocardium SUVmax at 1-hour strongly correlated with ECV (r = 0.91, P = 0.001), pre-contrast T1 map values (r = 0.66, P = 0.037), and left ventricle mass index (r = 0.80, P = 0.002) on CMR. SUVs derived from 99mTc-PYP scintigraphy with xSPECT/CT provides a discriminatory and quantitative method to diagnose and assess ATTR-CA burden. These findings strongly correlate with CMR.

Drug-resistant high grade glioma-related epilepsy surgery for focal motor status epilepticus localized by CT-PET imaging.

Tumor-related epilepsy is a frequent complication of glioblastoma with seizures often representing the first manifestation of the malignancy. Though tumor resection is associated with improved seizure control, extensive surgery is not always feasible if eloquent cortex is involved in seizure generation and early propagation. We describe a case of a patient with glioblastoma with drug-resistant focal status epilepticus where fluorodeoxyglucose positron emission tomography imaging was successfully used to localize the seizure-onset and optimize tumor resection. This led to successful resection of hypermetabolic tumor tissue and resolution of focal status epilepticus without damage to eloquent cortex.

Primary aortoenteric fistula: A case report and brief review of the literature.

Aortoenteric fistula is a life-threatening emergency and is associated with high morbidity and mortality. Prompt surgical intervention before the aneurysm ruptures lowers the mortality rate to about 50%. Potential imaging mimics for aortoenteric fistula include retroperitoneal fibrosis, mycotic aortic aneurysm, and infectious aortitis. Secondary aortoenteric fistula has relative higher incidence compared to primary and is more common with open aortic repair versus endovascular stent graft repair. Ectopic gas in the aneurysm sac and extravasation of enteric contrast into the aneurysm sac is diagnostic for aortoenteric fistula. However, enteric contrast is not recommended for routine evaluation of aortoenteric because the aforementioned finding is extremely rare. More common imaging findings include bowel loop appearing adherent to aneurysm sac with associated inflammatory stranding and foci or ectopic gas within the aneurysm sac or interposed between the bowel and aneurysm sac. Here we present a case of 52-year-old male who presents with incidental primary aortoenteric fistula.

A Prospective Trial Evaluating the Safety and Systemic Response From the Concurrent Use of Radiation Therapy with Checkpoint Inhibitor Immunotherapy in Metastatic Non-Small Cell Lung Cancer.

INTRODUCTION/BACKGROUND: This study assessed the safety and systemic (abscopal) response from the addition of local stereotactic body radiation therapy (SBRT) to checkpoint inhibitor (CPI) immunotherapy in patients with metastatic non-small cell lung cancer. PATIENTS/METHODS: Thirty-five patients with at least 2 sites of measurable disease on PET/CT received standard-of-care CPI immunotherapy alone (n = 19), or in combination with 4 cycles doublet carboplatin/pemetrexed chemotherapy (n = 16), and 3 to 5 fractions SBRT to a single extracranial target lesion between cycles 1 to 2 of the systemic therapy. Adverse events were assessed using CTCAE version 5.0. Best systemic objective response rate (ORR) was assessed using iRECIST criteria, excluding any irradiated lesion(s). Additional SBRT to a different target lesion was offered to patients who continued on immunotherapy with unconfirmed progressive disease or mixed response. RESULTS: Fifteen patients (44%) experienced 22 grade 1 to 2 toxicities potentially attributable to radiation, most commonly pneumonitis (n = 9) and fatigue (n = 6), and no grade 3 to 5 radiation-induced toxicities. Patients undergoing combined CPI-chemotherapy received a lower median biologically effective dose of SBRT than those undergoing CPI monotherapy (43.2 vs. 60Gy), but had a higher rate of radiation-induced toxicity (56% vs. 32%, P < .01). The best systemic ORR was 53%, with 20.5% stable disease and 26.5% progressive disease. Fifteen patients underwent a subsequent course of SBRT based on their response, among which 3 (20%) had progression-free intervals of 12, 16, and 10 months thereafter. CONCLUSIONS: Addition of SBRT to CPI immunotherapy (with/without chemotherapy) is safe. The favorable systemic response observed warrants further assessment with a randomized trial.

Imaging in Differentiating Cerebral Toxoplasmosis and Primary CNS Lymphoma With Special Focus on FDG PET/CT.

OBJECTIVE. The purpose of this article is to present a brief review of literature evaluating different imaging modalities with special focus on 18F-FDG PET/CT in differentiating cerebral toxoplasmosis and primary CNS lymphoma. CONCLUSION. Differentiating cerebral toxoplasmosis and primary CNS lymphoma is crucial in the care of patients with HIV infection. Delayed diagnosis can lead to considerable morbidity and mortality. The reference standard for diagnosis is biopsy and histopathologic examination. Biopsy has disadvantages due to its invasive nature and associated complications. Noninvasive imaging can be an alternative to biopsy for differentiation of toxoplasmosis and primary CNS lymphoma. Despite advances in MRI techniques, prophylaxis of opportunistic infection, and treatment of HIV infection, clinical situations continue to arise in which the diagnosis is not clear. In these instances, molecular imaging can be helpful.

Concept of an upright wearable positron emission tomography imager in humans.

BACKGROUND: Positron Emission Tomography (PET) is traditionally used to image patients in restrictive positions, with few devices allowing for upright, brain-dedicated imaging. Our team has explored the concept of wearable PET imagers which could provide functional brain imaging of freely moving subjects. To test feasibility and determine future considerations for development, we built a rudimentary proof-of-concept prototype (Helmet_PET) and conducted tests in phantoms and four human volunteers. METHODS: Twelve Silicon Photomultiplier-based detectors were assembled in a ring with exterior weight support and an interior mechanism that could be adjustably fitted to the head. We conducted brain phantom tests as well as scanned four patients scheduled for diagnostic F(18-) FDG PET/CT imaging. For human subjects the imager was angled such that field of view included basal ganglia and visual cortex to test for typical resting-state pattern. Imaging in two subjects was performed ~4 hr after PET/CT imaging to simulate lower injected F(18-) FDG dose by taking advantage of the natural radioactive decay of the tracer (F(18) half-life of 110 min), with an estimated imaging dosage of 25% of the standard. RESULTS: We found that imaging with a simple lightweight ring of detectors was feasible using a fraction of the standard radioligand dose. Activity levels in the human participants were quantitatively similar to standard PET in a set of anatomical ROIs. Typical resting-state brain pattern activation was demonstrated even in a 1 min scan of active head rotation. CONCLUSION: To our knowledge, this is the first demonstration of imaging a human subject with a novel wearable PET imager that moves with robust head movements. We discuss potential research and clinical applications that will drive the design of a fully functional device. Designs will need to consider trade-offs between a low weight device with high mobility and a heavier device with greater sensitivity and larger field of view.

Positron emission tomography in Warthin's tumor mimicking malignancy impacts the evaluation of head and neck patients.

PURPOSE: 1) To determine SUVs and PET/CT characteristics of Warthin's tumors in patients presenting to a head and neck cancer clinic. 2) To analyze the impact of PET/CT on the clinical course of these patients. MATERIALS AND METHODS: This is a single-institution retrospective analysis of patients with proven Warthin's tumors who underwent PET/CT done at or near the time of diagnosis and presented to a head and neck cancer practice. Data were obtained from the electronic medical records of these patients and the imaging and pathology databases. RESULTS: Six patients with Warthin's tumor met the criteria for and form the study cohort. Three patients had bilateral tumors. The SUVs for Warthin's varied from 3.4 to 16.1 in these patients, with an average of 7.8 and these SUVs were higher for Warthin's than for the cancers. These findings on PET/CT in this group required additional workup of all patients and required FNA, surgery or SPECT-CT to confirm the diagnosis. CONCLUSION: Although it is known that Warthin's tumor may be hypermetabolic on PET, this finding in the parotid or neck on PET/CT alters the evaluation and treatment of head and neck cancer patients and patients with cancers outside the head and neck by raising the concern about metastatic disease or multiple primary cancers. In other patients, PET/CT obtained for other reasons may prompt concern about incidental malignancy. This series specifically characterizes clinical features, SPECT-CT and FNA findings that can help reinforce the diagnosis of Warthin's and facilitate management.

Initial clinical test of a breast-PET scanner.

INTRODUCTION: The goal of this initial clinical study was to test a new positron emission/tomography imager and biopsy system (PEM/PET) in a small group of selected subjects to assess its clinical imaging capabilities. Specifically, the main task of this study is to determine whether the new system can successfully be used to produce images of known breast cancer and compare them to those acquired by standard techniques. METHODS: The PEM/PET system consists of two pairs of rotating radiation detectors located beneath a patient table. The scanner has a spatial resolution of ∼2 mm in all three dimensions. The subjects consisted of five patients diagnosed with locally advanced breast cancer ranging in age from 40 to 55 years old scheduled for pre-treatment, conventional whole body PET imaging with F-18 Fluorodeoxyglucose (FDG). The primary lesions were at least 2 cm in diameter. RESULTS: The images from the PEM/PET system demonstrated that this system is capable of identifying some lesions not visible in standard mammograms. Furthermore, while the relatively large lesions imaged in this study where all visualised by a standard whole body PET/CT scanner, some of the morphology of the tumours (ductal infiltration, for example) was better defined with the PEM/PET system. Significantly, these images were obtained immediately following a standard whole body PET scan. CONCLUSIONS: The initial testing of the new PEM/PET system demonstrated that the new system is capable of producing good quality breast-PET images compared standard methods.

Role of positron-emission tomography scan in the diagnosis and management of breast cancer.

Positron-emission tomography (PET) scan is a widely used imaging modality in the management of various malignancies. There is considerable controversy regarding its use in breast cancer diagnosis and treatment. In this review, we discuss published data on the use of 2-[18F]-fluoro-2-deoxy-D-glucose (FDG-PET) in the staging workup of locally advanced breast cancer, and management of locally recurrent and metastatic breast cancer. FDG-PET is a useful tool in staging advanced breast cancer and assessing the extent of disease involvement when metastasis is suspected. It might also aid in assessing early response to therapy. Future goals of improving PET scan accuracy in the management of breast cancer will be achieved through utilizing radiotracers, based on a better understanding of tumor biology and improvement in breast-specific PET scans.

The use of MR-myelography combining flexion and extension imaging in the diagnosis of cervical myelopathy: a case report.

This report describes the use of a non-invasive MR-Myelogram combining flexion and extension views to demonstrate causative factors in cervical myelopathy. Utilizing a new approach to MRI, mimicking an older technique of flexion/extension cervical myelography, we were able to identify the pathology of a patient suffering from progressive cervical myelopathy. We report a patient suffering from progressive multilevel cervical myelopathy due to posterior compression of the spinal cord by an inbuckling ligamentum flavum. Neutral position radiologic assessment failed to reveal any significant spinal cord compression. In this patient, the dynamic MRI and MR-Myelography was critical for demonstrating the posterior compression of the spinal cord by the ligamentum flavum. Flexion and extension MRI images of the cervical spine complemented by non-invasive MR-myelography were obtained. Surgical decompression was indicated based on these additional studies. The use of invasive myelography and in particular, flexion/extension myelography is in decline. MR-myelography combining flexion and extension views can be a useful noninvasive means of studying patients with possible ligamentous hypertrophy and dynamic cord compression.

Fluorodeoxyglucose-positron emission tomographic imaging for the diagnosis of mesial temporal lobe epilepsy.

OBJECTIVE: Fluorodeoxyglucose (FDG)-positron emission tomographic (PET) imaging plays an important role in the evaluation of intractable epilepsy. The metabolic defect has proven utility in the lateralization of temporal lobe epilepsy. However, the role of FDG-PET imaging in the localization of a seizure focus within the temporal lobe is uncertain. We evaluated FDG-PET imaging for the capability to localize a temporal seizure focus within the mesial structures. METHODS: Twenty-eight patients who underwent selective amygdalohippocampectomy for intractable temporal lobe epilepsy were studied. Patients were divided into 2 groups: those who were free of seizures (FS) and those with persisting seizures postoperatively. FS patients were defined by having mesial temporal lobe epilepsy (MTLE). Preoperative FDG-PET activity was evaluated in temporal lobe structures and contrasted with magnetic resonance imaging (MRI) for usefulness in identifying MTLE in an individual. RESULTS: Pathology of the hippocampus revealed mesial temporal sclerosis in all but 1 patient. Qualitative visual inspection of the MRI scan was not reliable in the identification of MTLE (P = 0.15). MRI volumetry found smaller mesial temporal structures (P = 0.04) in FS patients. Mesial temporal metabolic activity was reduced in the FS group (hippocampus, P = 0.001). However, a combination of imaging modalities was found to be the best predictor of MTLE. PET imaging plus MRI qualitative inspection identified all patients with and without MTLE correctly and was superior to MRI alone (P = 0.01 and P = 0.02, respectively). CONCLUSION: MRI volumetry and PET imaging were comparable (P = 0.73) and able to identify MTLE in most patients, but a combination of PET imaging and MRI visual inspection was superior in the recognition of MTLE.

Correlation among [18F]fluorodeoxyglucose positron emission tomography/computed tomography, cancer antigen 27.29, and circulating tumor cell testing in metastatic breast cancer.

BACKGROUND: Tumor marker cancer antigen (CA) 27.29 and combined [18F]-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) scans are used to follow up response to treatment and disease progression in patients with metastatic breast cancer (MBC). Recently, circulating tumor cell testing (CTC) has been used in this context. It is not known if 1 of the 3 tests can be a surrogate for another. PATIENTS AND METHODS: We analyzed a database of 35 patients with MBC. There were 173 time points (> or = 6 weeks apart) when > or = 2 of these tests were performed. Correlation among all the 3 tests was statistically analyzed. RESULTS: Results of PET/CT scans were compared with CA 27.29 at 163 time points. There was a statistically significant correlation between both groups (P = .02); however, sensitivity of CA 27.29 to detect metastatic disease observed on PET/CT scan was 59%. The results of PET/CT scans were compared with CTC at 93 events, where there was a statistically significant correlation between both groups (P = .0002); however, sensitivity of CTC to detect metastatic disease shown on PET/CT scans was 55%. Cancer antigen 27.29 results were also compared to CTC at 100 events, where there was a statistically significant correlation between both groups (P = .0002). However, only 64% of patients with high CA 27.29 had abnormal CTC. CONCLUSION: Our data shows correlation among PET/CT scan, CA 27.29, and CTC. However, both CA 27.29 and CTC had poor sensitivity and negative predictive value to detect metastatic disease observed on PET/CT scan. Normal CA 27.29 testing or CTC has to be interpreted cautiously in patients with MBC.

Management of cervical spine injuries in athletes.

OBJECTIVE: Although the incidence of catastrophic cervical spine injury in sport has been significantly reduced over the past 3 decades, the injury warrants continued attention because of the altered quality of life that often accompanies such an injury. The purpose of our literature review was to provide athletic trainers with an understanding of the mechanisms, anatomical structures, and complications often associated with sport-related cervical spine injury. We also present the most current recommendations for management and treatment of these potentially catastrophic injuries. DATA SOURCES: A review of the most pertinent literature between 1970 and 2005 was conducted using MEDLINE and the search terms spinal cord injury, cervical spine injury, neurosurgical trauma, cervical spinal stenosis, and catastrophic spine injury. DATA SYNTHESIS: Flexion of the head places the cervical spine into a straight line and prevents the neck musculature from assisting in force absorption. This mechanism is the primary cause of cervical fracture, dislocation, and quadriplegia. The most serious of the syndromes described in the literature involves a complete spinal cord injury with transverse myelopathy. This injury typically results in total loss of spinal function below the level of the lesion. CONCLUSIONS/RECOMMENDATIONS: Spinal trauma may result in a variety of clinical syndromes, according to the type and severity of the impact and bony displacement, as well as subsequent secondary insults such as hemorrhage, ischemia, and edema. Athletic trainers should be prepared to promptly recognize these potentially catastrophic injuries and follow the recommendations of the Inter-Association Task Force for the Appropriate Care of the Spine Injured Athlete in managing such injuries.

Simultaneous MRI and PET imaging of a rat brain.

Multi-modality imaging is rapidly becoming a valuable tool in the diagnosis of disease and in the development of new drugs. Functional images produced with PET fused with anatomical structure images created by MRI will allow the correlation of form with function. Our group is developing a system to acquire MRI and PET images contemporaneously. The prototype device consists of two opposed detector heads, operating in coincidence mode. Each MRI-PET detector module consists of an array of LSO detector elements coupled through a long fibre optic light guide to a single Hamamatsu flat panel position-sensitive photomultiplier tube (PSPMT). The use of light guides allows the PSPMTs to be positioned outside the bore of a 3T MRI scanner where the magnetic field is relatively small. To test the device, simultaneous MRI and PET images of the brain of a male Sprague Dawley rat injected with FDG were successfully obtained. The images revealed no noticeable artefacts in either image set. Future work includes the construction of a full ring PET scanner, improved light guides and construction of a specialized MRI coil to permit higher quality MRI imaging.

Direct carotid cavernous fistula in infancy: presentation and treatment.

An 11-month-old female patient presented with symptoms of orbital venous congestion. A CT scan showed enlarged superior ophthalmic vein and cavernous sinus on the symptomatic side. Catheter angiography confirmed a direct carotid-cavernous fistula with intra- and extracranial venous drainage. Successful coil embolization of the fistula was performed with resolution of the infant's symptoms and return of previously elevated intraocular pressures to normal. To our knowledge, no cases of carotid cavernous fistulas in infancy have been previously reported.