Early Brain Amyloid Accumulation at PET in Military Instructors Exposed to Subconcussive Blast Injuries.

Background Traumatic brain injury (TBI) is the leading cause of disability in young adults. Recurrent TBI is associated with a range of neurologic sequelae, but the contributing factors behind the development of such chronic encephalopathy are poorly understood. Purpose To quantify early amyloid ß deposition in the brain of otherwise healthy adult men exposed to repeated subconcussive blast injury using amyloid PET. Materials and Methods In this prospective study from January 2020 to December 2021, military instructors who were routinely exposed to repeated blast events were evaluated at two different points: baseline (before blast exposure from breacher or grenade) and approximately 5 months after baseline (after blast exposure). Age-matched healthy control participants not exposed to blasts and without a history of brain injury were evaluated at similar two points. Neurocognitive evaluation was performed with standard neuropsychologic testing in both groups. Analysis of PET data consisted of standardized uptake value measurements in six relevant brain regions and a whole-brain voxel-based statistical approach. Results Participants were men (nine control participants [median age, 33 years; IQR, 32-36 years] and nine blast-exposed participants [median age, 33 years; IQR, 30-34 years]; P = .82). In the blast-exposed participants, four brain regions showed significantly increased amyloid deposition after blast exposure: inferomedial frontal lobe (P = .004), precuneus (P = .02), anterior cingulum (P = .002), and superior parietal lobule (P = .003). No amyloid deposition was observed in the control participants. Discriminant analysis on the basis of regional changes of amyloid accumulation correctly classified the nine healthy control participants as healthy control participants (100%), and seven of the nine blast-exposed participants (78%) were correctly classified as blast exposed. Based on the voxel-based analysis, whole-brain parametric maps of early abnormal early amyloid uptake were obtained. Conclusion Early brain amyloid accumulation was identified and quantified at PET in otherwise healthy adult men exposed to repetitive subconcussive traumatic events. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Haller in this issue.

Interrogating the Role of Receptor-Mediated Mechanisms: Biological Fate of Peptide-Functionalized Radiolabeled Gold Nanoparticles in Tumor Mice.

To get a better insight on the transport mechanism of peptide-conjugated nanoparticles to tumors, we performed in vivo biological studies of bombesin (BBN) peptide functionalized gold nanoparticles (AuNPs) in human prostate tumor bearing mice. Initially, we sought to compare AuNPs with thiol derivatives of acyclic and macrocyclic chelators of DTPA and DOTA types. The DTPA derivatives were unable to provide a stable coordination of (67)Ga, and therefore, the functionalization with the BBN analogues was pursued for the DOTA-containing AuNPs. The DOTA-coated AuNPs were functionalized with BBN[7-14] using a unidentate cysteine group or a bidentate thioctic group to attach the peptide. AuNPs functionalized with thioctic-BBN displayed the highest in vitro cellular internalization (≈ 25%, 15 min) in gastrin releasing peptide (GRP) receptor expressing cancer cells. However, these results fail to translate to in vivo tumor uptake. Biodistribution studies following intravenous (IV) and intraperitoneal (IP) administration of nanoconjugates in tumor bearing mice indicated that the presence of BBN influences to some degree the biological profile of the nanoconstructs. For IV administration, the receptor-mediated pathway appears to be outweighed by the EPR effect. By contrast, in IP administration, it is reasoned that the GRPr-mediated mechanism plays a role in pancreas uptake.

Bimodal MRI/Fluorescence Nanoparticle Imaging Contrast Agent Targeting Prostate Cancer.

We developed a novel site-specific bimodal MRI/fluorescence nanoparticle contrast agent targeting gastrin-releasing peptide receptors (GRPrs), which are overexpressed in aggressive prostate cancers. Biocompatible ultra-small superparamagnetic iron oxide (USPIO) nanoparticles were synthesized using glucose and casein coatings, followed by conjugation with a Cy7.5-K-8AOC-BBN [7-14] peptide conjugate. The resulting USPIO(Cy7.5)-BBN nanoparticles were purified by 100 kDa membrane dialysis and fully characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, and magnetic resonance imaging (MRI) relaxivity, as well as evaluated for in vitro and in vivo binding specificity and imaging efficacy in PC-3 prostate cancer cells and xenografted tumor-bearing mice. The USPIO(Cy7.5)-BBN nanoparticles had a core diameter of 4.93 ± 0.31 nm and a hydrodynamic diameter of 35.56 ± 0.58 nm. The r2 relaxivity was measured to be 70.2 ± 2.5 s-1 mM-1 at 7T MRI. The Cy7.5-K-8AOC-BBN [7-14] peptide-to-nanoparticle ratio was determined to be 21:1. The in vitro GRPr inhibitory binding (IC50) value was 2.5 ± 0.7 nM, indicating a very high binding affinity of USPIO(Cy7.5)-BBN to the GRPr on PC-3 cells. In vivo MRI showed significant tumor-to-muscle contrast enhancement in the uptake group at 4 h (31.1 ± 3.4%) and 24 h (25.7 ± 2.1%) post-injection compared to the blocking group (4 h: 15.3 ± 2.0% and 24 h: -2.8 ± 6.8%; p < 0.005). In vivo and ex vivo near-infrared fluorescence (NIRF) imaging revealed significantly increased fluorescence in tumors in the uptake group compared to the blocking group. These findings demonstrate the high specificity of bimodal USPIO(Cy7.5)-BBN nanoparticles towards GRPr-expressing PC-3 cells, suggesting their potential for targeted imaging in aggressive prostate cancer.

Activity Within an Extraperitoneal Ureteral Herniation Detected on Bone Scan, Associated With a Partially Duplicated Collecting System.

A 64-year-old man with history of renal stones and prostate cancer presented for evaluation of osseous metastatic disease due to elevated prostate-specific antigen (13.7 ng/mL). A Tc-labeled bone scan demonstrated unusual linear uptake projecting over the lower pelvis extending into the scrotum. Follow-up CT confirmed a rare case of inguinoscrotal extraperitoneal herniation of the ureter associated with a partially duplicated left renal collecting system. The left-sided inguinoscrotal uptake was within the herniated ureter, potentially mimicking disease within the pelvis.

Reliability of Magnetic Resonance Spectroscopy and Positron Emission Tomography Computed Tomography in Differentiating Metastatic Brain Tumor Recurrence from Radiation Necrosis.

BACKGROUND: Clinical and/or neuroimaging changes after whole-brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) for metastatic brain tumor(s) present the clinical dilemma of differentiating tumor recurrence from radiation necrosis. Several imaging modalities attempt to answer this clinical question, including magnetic resonance spectroscopy (MRS) and positron emission tomography (PET) computed tomography (CT). We evaluated our experience regarding the ability of MRS and PET CT to differentiate tumor recurrence from radiation necrosis in patients who have received WBRT or SRS. METHODS: We retrospectively reviewed records of 242 patients with previous WBRT or SRS to identify those who had MRS and/or PET CT to differentiate tumor recurrence from radiation necrosis. Patients were sorted into true-positive, false-positive, false-negative, and true-negative groups on the basis of imaging interpretation and clinical course combined with surgical pathology results or reaction to nonsurgical treatments including SRS, dexamethasone, or observation. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were then calculated. RESULTS: Of 25 patients presenting such diagnostic questions, 19 were evaluated with MRS and 13 with PET CT. MRS sensitivity was 100%, specificity was 50%, and accuracy was 81.8%, whereas PET CT sensitivity was 36.4%, specificity was 66.7%, and accuracy was 42.9%. CONCLUSIONS: MRS has better accuracy than PET CT and a high negative predictive value, therefore making it more useful in distinguishing recurrent tumor from radiation necrosis. We encourage correlation with symptoms at imaging to aid in clinical decision making.

18F-FDG PET/CT total lesion glycolysis is associated with circulating tumor cell counts in patients with stage I to IIIA non-small cell lung cancer.

BACKGROUND: In non-small cell lung cancer (NSCLC), 18F-fluoro-2-deoxy-D-glucose (18F-FDG) uptake determined by PET and presence of circulating tumor cells (CTCs) in the peripheral blood independently predict outcomes. For 18F-FDG PET/CT staging interpretation, standardized uptake values (SUVmax/avg) are routinely used in clinical reporting. The goal was to investigate whether 18F-FDG uptake measured by SUVmax/avg, but also measures of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) (MTV × SUVavg), are associated with CTCs. METHODS: Prospectively, 7.5 mL blood was drawn from NSCLC patients at the time of staging 18F-FDG PET/CT and from healthy control subjects. CTCs were identified by immunofluorescent staining (CK8/18/19pos/EpCAMpos/CD45neg/DAPIpos nucleus). 18F-FDG PET/CTs were analyzed for SUVmax, SUVavg, MTV, and TLG. RESULTS: In 16 NSCLC patients with stage I-IIIA, MTV and TLG, in contrast to SUVmax and SUVavg, were positively associated with CTCs (linear regression analysis). No CTCs were detectable in 20 healthy control subjects. CONCLUSIONS: This pilot study demonstrates that 18F-FDG PET/CT TLG correlates with CTCs in NSCLC patients without distant metastases. TLG might be a more appropriate marker for hematogenous micrometastatic potential than SUVs.

Prognostic indicators of quality of life after cholecystectomy for biliary dyskinesia.

Approximately 30 per cent of patients who undergo cholecystectomy for biliary dyskinesia will continue to have symptoms after surgery. Quality of life has not been evaluated but may be decreased in these patients. The purpose of this study was to measure quality of life after laparoscopic cholecystectomy in these patients to better define optimal treatment of biliary dyskinesia. All patients with biliary dyskinesia (defined as the absence of gallstones, and a gallbladder ejection fraction of <35%) who underwent cholecystectomy at our institution from January 31, 2000 to January 31, 2005 were identified. Preoperative data including ultrasound, biochemical data, and pathology were retrieved by chart review. Postoperative assessment included the Gastrointestinal Quality of Life Index and a symptom survey. The postoperative quality of life was compared with historic standards. The quality of life was also compared with preoperative variables to determine if any variables predicted outcome. A total of 66 patients were identified as fitting the inclusion criteria. Forty-three patients were reached by phone and 30 agreed to participate. Patients were noted to have good recall as to preoperative symptoms when the retrospective survey of symptoms was compared with the medical record. The mean +/- SD postoperative quality of life in the study population was 113 +/- 20. This is higher than in historic patients with gallbladder disease before (84 +/- 19) and after (102 +/- 13) cholecystectomy. Quality of life in the study group was lower than the healthy control (125 +/- 13). Patients having both postprandial nausea and vomiting before surgery had a lower quality of life (P < 0.029) after surgery as compared with those without these preoperative symptoms. When adjusted for nausea and vomiting, the quality of life in study patients (119 +/- 14) was similar to normal controls. No other symptom, laboratory, pathologic, or sonographic data were predictive of a lower quality of life. Cholecystectomy is beneficial for most patients with biliary dyskinesia. Nausea and vomiting were negative predictors of quality of life after cholecystectomy. These patients with nausea and vomiting may have a global gastrointestinal motility disorder and are less likely to benefit from cholecystectomy.

Focal hepatic activity during ventilation-perfusion scintigraphy due to systemic-portal shunt due to superior vena cava obstruction from histoplasmosis-induced fibrosing mediastinitis.

A 59-year-old woman with a history of fibrosing mediastinitis secondary to histoplasmosis diagnosed on mediastinoscopy presented with dyspnea. A ventilation-perfusion scan demonstrated decreased perfusion to the entire right lung. In addition, the perfusion images demonstrated focal abnormal activity in part of the liver. On computed tomography of the chest, there was significant soft tissue opacification in the mediastinum occluding the right pulmonary artery, with passage of the injected contrast via collateral vessels to the liver. The main collateral pathway was via the right internal thoracic vein and the umbilical vein. Pulmonary angiography confirmed complete occlusion of the right pulmonary artery.

Clinical significance of rapid (accelerated) gastric emptying.

PURPOSE: The purpose of this study was to determine the significance and frequency of rapid gastric emptying (RGE) in clinical practice and to examine its relationship to age, gender, and presenting symptoms. METHODS: The review included 750 patients who underwent scintigraphic gastric emptying studies (GES) within the past 11 years. In 80 patients with RGE, the mean gastric emptying time (GET) in female and male patients was compared with study gender differences. Similarly, the mean GET in young and old patients was compared with study age differences. The presenting symptoms and conditions indicating GES were noted. RESULTS: RGE was found in 80 of 750 study patients (10.7%). RGE was equally common in both sexes. Younger patients (mean age, 34.3 +/- 9.5 years) and older patients (mean age, 67.3 +/- 11.6 years) had similar mean GETs. Most patients with RGE presented with symptoms that mimicked gastroparesis. CONCLUSIONS: RGE has no relationship to age or gender. RGE may be representative of early dumping syndrome in most patients. GES help make a clear distinction between early dumping syndrome and gastroparesis, which can present with similar symptoms.

Interrelationship of homocysteine-cobalamin-folate indices in human subjects of various ages: can hyper-homocyteinemia be relieved with B-12 supplementation?

OBJECTIVE: To find the effect of aging, nutrition, and gender on Homocysteine-Cobalamin-Folate (HCF) Triad and to determine if B-12 supplementation decreases high levels of homocysteine. METHODS: In 192 subjects, blood indices were determined to study the relationship of HCF triad to age and gender, 28 had low holotranscobalmin (TC II), and five had low serum cobalamin. Thirty-nine of the subjects who had hyperhomocysteinemia were daily given 100 mcg B-12 for three months. RESULTS: Thirty-six subjects with hyperhomocysteinemia exhibited different responses based on baseline serum B-12 levels. Those with serum B-12 < 350 pg/ml decreased homocysteine and increased red blood cell (RBC) folate. The serum folate was not significantly changed. Those with B-12 > 350 pg/ml exhibited increase in RBC folate only. CONCLUSION: B-12 supplementation is effective in alleviating hyperhomocysteinemia. Compared to men, aging women had lower homocysteine.

Banding and Step-Stair Artifacts on the Cardiac-CT Caused By Pseudo-Ectopic Beats.

Step-stair and banding artifacts may result from irregular ventricular rhythm caused by atrial fibrillation or premature ectopic ventricular contractions. In the case reported here, severe banding and misalignment artifacts occurred due to electrocardiographic noise mimicking ectopic beats. Severe EKG noise or pseudo-ectopic beats may cause rare but serious artifacts during cardiac-CT acquisition. Vendor-provided software for correcting ectopic beats can be used to remove pseudo-ectopic beats and eliminate artifacts caused by the EKG noise. All efforts should be made to prevent this kind of problem from happening in the first place.

Scintigraphic Demonstration of Calciphylaxis.

We report the case of a 59-year-old woman with end-stage renal disease who presented with bilateral medial calf tenderness and subsequent development of a large necrotic plaque that was proven at biopsy to be calciphylaxis. A radionuclide bone scan contributed to management by helping establish the diagnosis. Calciphylaxis is a highly morbid small vessel vasculopathy encountered in patients on hemodialysis. Early recognition and proper management may improve outcomes.

Determining functional significance of subclavian artery stenosis using exercise thallium-201 stress imaging.

Subclavian artery stenosis (SAS) is a rare lesion accounting for nearly 2.5% of all extracranial arterial occlusions. Symptoms from SAS usually relate to subclavian steal, and include syncope, vertigo, ataxia, and, rarely, upper limb paralysis or hemipareses. Upper extremity ischemia may result in intermittent or constant arm pain. The majority of patients with SAS are asymptomatic. Upper extremity ischemia is particularly unusual. More commonly, patients with significant SAS have symptoms of cerebral ischemia, which are usually triggered by vigorous motion of the arm on the side of the severe proximal subclavian obstruction. Stress exercise radionuclide imaging appears to be a valuable modality in determining the functional significance of SAS. We describe a case in which radionuclide imaging with thallium-201 after stress of the upper extremities was used for risk stratification of subclavian stenosis, and to help decide treatment options.

Complementary role of positron emission tomography in merkel cell carcinoma.

Merkel cell carcinoma is a rare type of neuroendocrine tumor of the skin with approximately 470 documented new cases annually in the United States. These tumors have high metastatic and recurrence rates, making them aggressive and difficult to treat. Diagnostic workup usually includes computed tomography, magnetic resonance imaging, and scintigraphy methods such as octreotide scans. More recently, positron emission tomographic scanning has been used to evaluate Merkel cell carcinomas. A case of Merkel cell carcinoma, in which positron emission tomography imaging with fluorodeoxyglucose played an important role in staging, re-staging, and identifying previously unknown distant metastatic disease, is presented in this article.

Determination of death by neurological criteria.

Until 1968, when an ad hoc Harvard Medical School Committee published a landmark paper calling for determination of death using neurological rather than cardiovascular criteria, death was considered to have occurred when the heart irreversibly ceased beating. Since that time, every jurisdiction in the country has come to accept through law or court decision neurological criteria to define death. The authors review the issue of death by neurological criteria in light of current guidelines and recent advances.