Steven Burrell

Early Detection of Cerebral Glucose Uptake Changes in the 5XFAD Mouse

Brain glucose hypometabolism has been observed in Alzheimer’s disease (AD) patients, and is detected with 18F radiolabelled glucose, using positron emission tomography. A pathological hallmark of AD is deposition of brain β-amyloid plaques that may influence cerebral glucose metabolism. The five times familial AD (5XFAD) mouse is a model of brain amyloidosis exhibiting AD-like phenotypes. This study examines brain β-amyloid plaque deposition and 18FDG uptake, to search for an early biomarker distinguishing 5XFAD from wild-type mice. Thus, brain 18FDG uptake and plaque deposition was studied in these mice at age 2, 5 and 13 months. The 5XFAD mice demonstrated significantly reduced brain 18FDG uptake at 13 months relative to wild-type controls but not in younger mice, despite substantial β-amyloid plaque deposition. However, by comparing the ratio of uptake values for glucose in different regions in the same brain, 5XFAD mice could be distinguished from controls at age 2 months. This method of measuring altered glucose metabolism may represent an early biomarker for the progression of amyloid deposition in the brain. We conclude that brain 18FDG uptake can be a sensitive biomarker for early detection of abnormal metabolism in the 5XFAD mouse when alternative relative uptake values are utilized.

2-Deoxy-2-(F-18)fluoro-D-glucose—Positron Emission Tomography of the Head and Neck: An Atlas of Normal Uptake and Variants

In the evaluation of tumors of the head and neck region, positron emission tomography (PET) using 2-deoxy-2-[F-18]fluoro-d-glucose (FDG) is increasingly playing a valuable clinical role. However, assessment of this region can be challenging because of the large number of structures in this area which may demonstrate physiologically increased uptake of FDG. Furthermore, these structures are generally small, and uptake patterns can be quite variable, rendering the head and neck region one of the most difficult areas of the body to assess with FDG-PET. To assist in this endeavor, a pictorial of normal FDG uptake, including commonly encountered variants, is presented.

Positron Emission Tomography/Computed Tomography for the Diagnosis and Assessment of Giant Cell Arteritis: When to Consider It and Why

Large-vessel involvement is now well recognized in patients with giant cell arteritis (GCA). While exact numbers vary, a recent study demonstrated that up to 67.5% of patients with biopsy-proven GCA have large-vessel disease at the time of diagnosis1. On occasion, large-vessel arteritis may occur in isolation, without classical features such as headache and scalp tenderness, making a clinical diagnosis difficult2. Recognition, however, remains important, as mortality in this subset of patients is significantly increased3. While temporal artery biopsy remains the diagnostic gold standard in GCA, it may be falsely negative in 42% of patients with isolated large artery disease2. In such cases, imaging studies are necessary to confirm large-vessel vasculitis. Angiography is suboptimal because of its invasive nature, risks of contrast allergy and nephropathy, and ability to detect only late anatomical changes such as stenosis or aneurysm. Positron emission tomography/computed tomography (PET/CT) is an alternative, offering the ability to detect both structural lesions and active inflammation. When inflammatory cells become activated, they undergo a “respiratory burst” and metabolize large amounts of glucose4. (18F) fluorodeoxyglucose (FDG) PET is a nuclear medicine scan that uses a glucose analog labeled with radioactive fluorine-18, which is taken into cells through the glut-1-transporter. This tracer mimics the distribution of glucose, thereby identifying conditions with high glucose metabolism, such as malignancy, infection, and inflammation5. Current PET scans are often combined with a low-dose CT scan for enhanced anatomical localization of isotope. While used most commonly for oncologic detection and staging, PET/CT is gaining popularity for use in a number of inflammatory diseases, and has notable advantages for the diagnosis of large-vessel arteritis. PET/CT identifies active inflammation within the arterial wall, potentially leading to an earlier diagnosis of GCA. Studies of small numbers of … Address correspondence to Dr. J.G. Hanly, Division of Rheumatology, Nova Scotia Rehabilitation Centre (2nd Floor), 1341 Summer Street, Halifax, Nova Scotia B3H 4K4, Canada. E-mail: john.hanly{at}cdha.nshealth.ca

Atypical Femoral Fractures: A Teaching Perspective

This article provides an overview of atypical femoral fractures with a highlight on their radiographic findings. Potent antiresorptive agents such as bisphosphonates or denosumab have been associated with the development of such fractures. However, at this time, a causal association has not been conclusively established. Atypical femoral fractures are insufficiency fractures, which frequently present with bone pain. Early identification of characteristic radiographic features and withdrawal of antiresorptive therapy may prevent the development of completed atypical femoral fractures.

Laparoscopic accessory splenectomy: the value of perioperative localization studies

BackgroundLaparoscopic splenectomy is an effective treatment for many patients with immune thrombocytopenic purpura (ITP) who fail or relapse after treatment with steroids. Patients with an incomplete response to splenectomy and those who experience recurrence of symptoms should be evaluated for the presence of an accessory spleen. The clinical effectiveness of laparoscopic excision of an accessory spleen after a previous splenectomy for ITP has varied in different studies. Laparoscopic intraoperative identification of an accessory spleen can be difficult. The authors report their experience with laparoscopic accessory splenectomy (LAS) and the use of perioperative localization methods for this procedure.MethodsThis study reviewed seven consecutive patients who underwent LAS, after initial splenectomy failed to cure ITP, at a tertiary care center between April 9, 2003 and March 31, 2008. Demographics, diagnostic and localization studies, technical success, and the effect on thrombocytopenia were examined. The location of the accessory spleen also was recorded. A novel method for localizing accessory spleen was used. It consisted of preoperative computed tomography (CT)-guided injection of methylene blue at the accessory spleen’s site, preoperative intravenous injection of 99m-technetium-labeled, heat-damaged red blood cells, or both. Intraoperatively, the dye was used for visual identification, and the gamma probe was used to aid in locating and confirming the presence of the accessory spleen in the excised specimen.ResultsSeven patients with recurrent ITP after initial failed splenectomy underwent LAS during the study period. Five of these patients had the initial splenectomy performed laparoscopically. All seven patients had successful laparoscopic removal of the accessory spleen based on a final pathologic examination. One patient required the second laparoscopic exploration with perioperative localization after a failed attempt without it. These perioperative localization methods were used in subsequent operations on other patients. These methods were found to be helpful in the intraoperative identification of the accessory spleens. The accessory spleens missed at initial splenectomy were found in unusual locations. Five of the seven patients had sustained improvement in platelet counts after LAS. One patient had a postoperative ileus that resolved with nonoperative management. No other complications or mortality was observed.ConclusionThe LAS procedure after previous splenectomy is feasible and safe. Perioperative localization methods aid in the intraoperative identification of an accessory spleen. Accessory spleens missed at initial splenectomy are generally found in unusual locations. Treatment of recurrent or unresolved ITP with LAS can be effective for some patients.

Synthesis and Preliminary Evaluation of Piperidinyl and Pyrrolidinyl Iodobenzoates as Imaging Agents for Butyrylcholinesterase

PurposeThe purpose of this study is to synthesize and evaluate specific agents for molecular imaging of butyrylcholinesterase (BuChE), known to be associated with neuritic plaques and neurofibrillary tangles in Alzheimer’s disease (AD). In this study, these agents were tested in a normal rat model. The distribution of radiolabel was compared with known BuChE histochemical distribution in the rat brain.ProceduresIodobenzoate esters were synthesized and tested, through spectrophotometric analysis, as specific substrates for BuChE. These compounds were converted to the corresponding 123I esters from tributyltin intermediates and purified for studies in the rat model. Whole body dynamic scintigraphic images were obtained for biodistribution studies. Autoradiograms of brain sections were obtained and compared to histochemical distribution of the enzyme in this model system.ResultsThe three iodobenzoate esters studied were specific substrates for BuChE. Whole body biodistribution studies with 123I-labeled compounds showed rapid disappearance from the body while radioactivity was retained in the head region. Brain section autoradiography of animals injected with these labeled compounds indicated that most areas known to contain BuChE corresponded to areas of radioactivity accumulation.ConclusionBuChE-specific radiolabeled iodobenzoates enter the brain and, in general, label areas known to exhibit BuChE activity in histochemical studies. Such molecules may represent a new direction for the development of agents for the molecular imaging of BuChE in the living brain, especially in regions where BuChE-containing neuropathological structures appear in AD.

Positron Emission Tomography/Computerized Tomography in Newly Diagnosed Patients with Giant Cell Arteritis Who Are Taking Glucocorticoids

Objective. Large vessel uptake on positron emission tomography/computerized tomography (PET/CT) supports the diagnosis of giant cell arteritis (GCA). Its value, however, in patients without arteritis on temporal artery biopsy and in those receiving glucocorticoids remains unknown. We compared PET/CT results in GCA patients with positive (TAB+) and negative temporal artery biopsies (TAB−), and controls. Methods. Patients with new clinically diagnosed GCA starting treatment with glucocorticoids underwent temporal artery biopsy and PET/CT. Using a visual semiquantitative approach, 18F-fluorodeoxyglucose (FDG) uptake was scored in 8 vascular territories and summed overall to give a total score in patients and matched controls. Results. Twenty-eight patients with GCA and 28 controls were enrolled. Eighteen patients with GCA were TAB+. Mean PET/CT scores after an average of 11.9 days of prednisone were higher in patients with GCA compared to controls, for both total uptake (10.34 ± 2.72 vs 7.73 ± 2.56; p = 0.001), and in 6 of 8 specific vascular territories. PET/CT scores were similar between TAB+ and TAB− patients with GCA. The optimal cutoff for distinguishing GCA cases from controls was a total PET/CT score of ≥ 9, with an area under the receiver-operating characteristic curve of 0.75, sensitivity 71.4%, and specificity 64.3%. Among patients with GCA, these measures correlated with greater total PET/CT scores: systemic symptoms (p = 0.015), lower hemoglobin (p = 0.009), and higher platelet count (p = 0.008). Conclusion. Vascular FDG uptake scores were increased in most patients with GCA despite exposure to prednisone; however, the sensitivity and specificity of PET/CT in this setting were lower than those previously reported.

A prospective cohort study of the feasibility and efficacy of iron reduction by phlebotomy in recipients of hematopoietic SCT

Transfusional iron overload is common in hematopoietic SCT (HSCT) patients and is a potential cause of morbidity and mortality. Iron overload, estimated by increased ferritin, appears to be associated with adverse outcomes and decreased survival.1, 2, 3, 4

Peripheral dysgraphia: dissociations of lowercase from uppercase letters and of print from cursive writing.

Clinical analyses of patients with acquired dysgraphia provide unique opportunities to understand the cognitive and neural organization of written language production. We report J.B., a 50-year-old woman with peripheral dysgraphia who had prominent dissociations in her ability to write in lowercase versus uppercase and print versus cursive. We gave J.B. a series of tasks that evaluated her skills at writing uppercase and lowercase print and cursive, spelling aloud and in writing, writing numbers and symbols, and visual letter recognition and imagery. She was impaired in printing letters, with lowercase more affected than uppercase, but her cursive writing was relatively intact. This pattern was consistent across letter, word, and nonword writing tasks. She was unimpaired on tasks assessing her visual recognition and imagery of lowercase and uppercase letters. Her writing of numbers was preserved. J.B.s handwriting disorder was accompanied by a central phonological dysgraphia. Our findings indicate functional independence of graphomotor programs for print and cursive letter styles and for letters and numbers. We discuss the relationship between peripheral and central writing disorders.

Improving Management of Osteoporosis Through Simple Changes in Reporting Fragility Fractures

Fragility fractures represent a major health care issue that is associated with substantial morbidity, mortality, and health care costs. Pharmacologic therapy is effective in lowering the risk of further fractures by 30%-70%, but there is a major care gap, as <20% of patients with fragility fractures are started on pharmacotherapy [1]. Radiologists are in a key position to close the care gap by implementing simple changes in reporting (Figure 1). The Canadian Association of Radiologists (CAR) and Osteoporosis Canada (OC) have joined forces to promote these initiatives. A fragility fracture may be defined as a fracture that occurs spontaneously or after minor trauma, such as a fall from standing height or less, excluding craniofacial, hand, ankle, and foot fractures [2]. Individuals over the age of 50 years who have sustained a fragility fracture of the spine, hip, proximal humerus, or forearm are at particularly increased risk of future fractures (>20% 10-year risk for hip and spine fractures) and management in accordance with OC guidelines is indicated.