Imaging Aspects of the Hippocampus.

The hippocampus is one of the most sophisticated structures in the brain, owing to its complex anatomy, intriguing functions, relationship with other structures, and relevant associated symptoms. Despite being a structure analyzed for centuries, its anatomy and physiology in the human body are still being extensively studied, as well as associated pathologic conditions and potential biomarkers. It can be affected by a broad group of diseases that can be classified as congenital, degenerative, infectious or inflammatory, neoplastic, vascular, or toxic-metabolic disease. The authors present the anatomy and close structures, function, and development of the hippocampus, as well as an original algorithm for imaging diagnosis. The algorithm includes pathologic conditions that typically affect the hippocampus and groups them into nodular (space occupying) and nonnodular pathologic conditions, serving as a guide to narrow the differential diagnosis. MRI is the imaging modality of choice for evaluation of the hippocampus, and CT and nuclear medicine also improve the analysis. The MRI differential diagnosis depends on anatomic recognition and careful characterization of associated imaging findings such as volumetric changes, diffusion restriction, cystic appearance, hyperintensity at T1-weighted imaging, enhancement, or calcification, which play a central role in diagnosis along with clinical findings. Some pathologic conditions arising from surrounding structures such as the amygdala are also important to recognize. Pathologic conditions of the hippocampus can be a challenge to diagnose because they usually manifest as similar clinical syndromes, so the imaging findings play a potential role in guiding the final diagnosis. Online supplemental material is available for this article. ©RSNA, 2022.

Theranostics in Nuclear Medicine: Emerging and Re-emerging Integrated Imaging and Therapies in the Era of Precision Oncology.

Theranostics refers to the pairing of diagnostic biomarkers with therapeutic agents that share a specific target in diseased cells or tissues. Nuclear medicine, particularly with regard to applications in oncology, is currently one of the greatest components of the theranostic concept in clinical and research scenarios. Theranostics in nuclear medicine, or nuclear theranostics, refers to the use of radioactive compounds to image biologic phenomena by means of expression of specific disease targets such as cell surface receptors or membrane transporters, and then to use specifically designed agents to deliver ionizing radiation to the tissues that express these targets. The nuclear theranostic approach has sparked increasing interest and gained importance in parallel to the growth in molecular imaging and personalized medicine, helping to provide customized management for various diseases; improving patient selection, prediction of response and toxicity, and determination of prognosis; and avoiding futile and costly diagnostic examinations and treatment of many diseases. The authors provide an overview of theranostic approaches in nuclear medicine, starting with a review of the main concepts and unique features of nuclear theranostics and aided by a retrospective discussion of the progress of theranostic agents since early applications, with illustrative cases emphasizing the imaging features. Advanced concepts regarding the role of fluorine 18-fluorodeoxyglucose PET in theranostics, as well as developments in and future directions of theranostics, are discussed. ©RSNA, 2020 See discussion on this article by Greenspan and Jadvar.

Young-Onset Alzheimer Dementia Due to a Novel Pathogenic Presenilin 1 Variant Initially Misdiagnosed as Autoimmune Encephalitis.

OBJECTIVES: Pathogenic variants in presenilin 1 (PSEN1) are related to early-onset Alzheimer disease (AD) and may occur as de novo variants. In comparison with sporadic forms, it can present with psychiatric manifestations, seizures, myoclonus, and focal presentation. Because PSEN1 can occur in young patients who lack a family history of neurologic disorders and because these symptoms are also frequent in autoimmune encephalitis (AE), diagnosis may be overlooked. Our aim was to demonstrate the challenge in diagnosing young patients with neurodegenerative diseases that simulate AE. METHODS: We describe a case of a young patient with insidious progressive dementia, myoclonus, seizures, and aphasia, with no family history of dementia, along with signs suggestive of neuroinflammation on brain MRI and CSF examination. RESULTS: She was initially misdiagnosed as having AE. Further investigation was performed, leading to the discovery of a novel and de novo pathogenic variant in PSEN1. DISCUSSION: This case demonstrates the importance of considering PSEN1 in young patients with insidious progressive dementia with atypical clinical and neuroimaging features, even in patients without a family history of neurologic disorders. Not adhering to published criteria of possible and probable AE and overinterpretation of subtle inflammatory findings in CSF and MRI contribute to misdiagnosis.

Amyloid profile is associated with sleep quality in preclinical but not in prodromal Alzheimer's disease older adults.

BACKGROUND: Few studies have assessed whether neuropathological markers of AD in the preclinical and prodromal stages are associated with polysomnographic changes and obstructive sleep apnea (OSA). METHODS: This was a cross-sectional, case-control study of older adults (≥60 years) without relevant clinical and psychiatric comorbidities selected randomly from a cohort of individuals without dementia in a tertiary university hospital in São Paulo, Brazil. They underwent neuropsychological evaluation for clinical diagnosis and were allocated into two samples: cognitively unimpaired (CU) and mild cognitive impairment (MCI). Also, they underwent PET-PiB to determine the amyloid profile and all-night in-lab polysomnography. For each sample, we compared polysomnographic parameters according to the amyloid profile (A+ vs A-). RESULTS: We allocated 67 participants (mean age 73 years, SD 10,1), 70 % females, 14 ± 5 years of education, into two samples: CU (n = 28, 42.4 %) and MCI (n = 39, 57.6 %). In the CU sample, the group A+ (n = 9) showed worse sleep parameters than A- (n = 19) (lower total sleep time (p = 0.007), and sleep efficiency (p = 0.005); higher sleep onset latency (p = 0.025), wake time after sleep onset (p = 0.011), and arousal index (AI) (p = 0.007)), and changes in sleep structure: higher %N1 (p = 0.005), and lower %REM (p = 0.006). In the MCI sample, MCI A-had higher AI (p = 0.013), respiratory disturbance index (p = 0.025, controlled for age), and higher rates of severe OSA than A+. DISCUSSION: The amyloid profile was associated with polysomnographic markers of worse sleep quality in individuals with preclinical AD but not with prodromal AD, probably due to the higher frequencies of severe OSA.

Does TRODAT-1 SPECT Uptake Correlate with Cerebrospinal Fluid α-Synuclein Levels in Mid-Stage Parkinson's Disease?

BACKGROUND: Parkinson's disease (PD) is characterized by a progressive loss of nigrostriatal dopaminergic neurons with impaired motor and non-motor symptoms. It has been suggested that motor asymmetry could be caused due to an imbalance in dopamine levels, as visualized by dopamine transporter single emission computed tomography test (DAT-SPECT), which might be related to indirect measures of neurodegeneration, evaluated by the Montreal Cognitive Assessment (MOCA) and α-synuclein levels in the cerebrospinal fluid (CSF). Therefore, this study aimed to understand the correlation between disease laterality, DAT-SPECT, cognition, and α-synuclein levels in PD. METHODS: A total of 28 patients in the moderate-advanced stage of PD were subjected to neurological evaluation, TRODAT-1-SPECT/CT imaging, MOCA, and quantification of the levels of α-synuclein. RESULTS: We found that α-synuclein in the CSF was correlated with global cognition (positive correlation, r2 = 0.3, p = 0.05) and DAT-SPECT concentration in the putamen (positive correlation, r2 = 0.4, p = 0.005), and striatum (positive correlation, r2 = 0.2, p = 0.03), thus working as a neurodegenerative biomarker. No other correlations were found between DAT-SPECT, CSF α-synuclein, and cognition, thus suggesting that they may be lost with disease progression. CONCLUSIONS: Our data highlight the importance of understanding the dysfunction of the dopaminergic system in the basal ganglia and its complex interactions in modulating cognition.

General Concepts in Theranostics.

Theranostics describes the pairing of diagnostic biomarkers and therapeutic agents with common specific targets. Nuclear medicine is the greatest theranostics protagonist, relying on radioactive tracers for imaging biologic phenomena and delivering ionizing radiation to the tissues that take up those tracers. The concept has gained importance with the growth of personalized medicine, allowing customized management for diseases, refining patient selection, better predicting responses, reducing toxicity, and estimating prognosis. This work provides an overview of the general concepts of the theranostics approach in nuclear medicine discussing its background, features, and future directions in imaging and therapy.

Subjective sleep parameters in prodromal Alzheimer's disease: a case-control study.

OBJECTIVE: People with Alzheimer's disease (AD) dementia have impaired sleep. However, the characteristics of sleep in the early stages of AD are not well known, and studies with the aid of biomarkers are lacking. We assessed the subjective sleep characteristics of non-demented older adults and compared their amyloid profiles. METHODS: We enrolled 30 participants aged ≥ 60 years, with no dementia or major clinical and psychiatric diseases. They underwent [11C]PiB-PET-CT, neuropsychological evaluations, and completed two standardized sleep assessments (Pittsburgh Sleep Quality Inventory and Epworth Sleep Scale). RESULTS: Comparative analysis of subjective sleep parameters across the two groups showed longer times in bed (p = 0.024) and reduced sleep efficiency (p = 0.05) in individuals with positive amyloid. No differences in other subjective sleep parameters were observed. We also found that people with multiple-domain mild cognitive impairment (MCI) had shorter self-reported total sleep times (p = 0.034) and worse overall sleep quality (p = 0.027) compared to those with single-domain MCI. CONCLUSIONS: Older adults testing positive for amyloid had a longer time in bed and lower sleep efficiency, regardless of cognitive status. In parallel, individuals with multiple-domain MCI reported shorter sleep duration and lower overall sleep quality.

Topography of 11C-Pittsburgh compound B uptake in Alzheimer's disease: a voxel-based investigation of cortical and white matter regions.

OBJECTIVE: To compare results of positron emission tomography (PET) with carbon-11-labeled Pittsburgh compound B (11C-PIB) obtained with cerebellar or global brain uptake for voxel intensity normalization, describe the cortical sites with highest tracer uptake in subjects with mild Alzheimer's disease (AD), and explore possible group differences in 11C-PIB binding to white matter. METHODS: 11C-PIB PET scans were acquired from subjects with AD (n=17) and healthy elderly controls (n=19). Voxel-based analysis was performed with statistical parametric mapping (SPM). RESULTS: Cerebellar normalization showed higher 11C-PIB uptake in the AD group relative to controls throughout the cerebral cortex, involving the lateral temporal, orbitofrontal, and superior parietal cortices. With global uptake normalization, greatest cortical binding was detected in the orbitofrontal cortex; decreased 11C-PIB uptake in white matter was found in the posterior hippocampal region, corpus callosum, pons, and internal capsule. CONCLUSION: The present case-control voxelwise 11C-PIB PET comparison highlighted the regional distribution of amyloid deposition in the cerebral cortex of mildly demented AD patients. Tracer uptake was highest in the orbitofrontal cortex. Decreased 11C-PIB uptake in white-matter regions in this patient population may be a marker of white-matter damage in AD.

Colorectal cancer staging: comparison of whole-body PET/CT and PET/MR.

PURPOSE: Correct staging is imperative for colorectal cancer (CRC) since it influences both prognosis and management. Several imaging methods are used for this purpose, with variable performance. Positron emission tomography-magnetic resonance (PET/MR) is an innovative imaging technique recently employed for clinical application. The present study was undertaken to compare the staging accuracy of whole-body positron emission tomography-computed tomography (PET/CT) with whole-body PET/MR in patients with both newly diagnosed and treated colorectal cancer. METHODS: Twenty-six patients, who underwent same day whole-body (WB) PET/CT and WB-PET/MR, were evaluated. PET/CT and PET/MR studies were interpreted by consensus by a radiologist and a nuclear medicine physician. Correlations with prior imaging and follow-up studies were used as the reference standard. Correct staging was compared between methods using McNemar's Chi square test. RESULTS: The two methods were in agreement and correct for 18/26 (69%) patients, and in agreement and incorrect for one patient (3.8%). PET/MR and PET/CT stages for the remaining 7/26 patients (27%) were discordant, with PET/MR staging being correct in all seven cases. PET/MR significantly outperformed PET/CT overall for accurate staging (P = 0.02). CONCLUSION: PET/MR outperformed PET/CT in CRC staging. PET/MR might allow accurate local and distant staging of CRC patients during both at the time of diagnosis and during follow-up.

Subjective sleep parameters in prodromal Alzheimer's disease: a case-control study

Objective: People with Alzheimer's disease (AD) dementia have impaired sleep. However, the characteristics of sleep in the early stages of AD are not well known, and studies with the aid of biomarkers are lacking. We assessed the subjective sleep characteristics of non-demented older adults and compared their amyloid profiles. Methods: We enrolled 30 participants aged ≥ 60 years, with no dementia or major clinical and psychiatric diseases. They underwent [11C]PiB-PET-CT, neuropsychological evaluations, and completed two standardized sleep assessments (Pittsburgh Sleep Quality Inventory and Epworth Sleep Scale). Results: Comparative analysis of subjective sleep parameters across the two groups showed longer times in bed (p = 0.024) and reduced sleep efficiency (p = 0.05) in individuals with positive amyloid. No differences in other subjective sleep parameters were observed. We also found that people with multiple-domain mild cognitive impairment (MCI) had shorter self-reported total sleep times (p = 0.034) and worse overall sleep quality (p = 0.027) compared to those with single-domain MCI. Conclusions: Older adults testing positive for amyloid had a longer time in bed and lower sleep efficiency, regardless of cognitive status. In parallel, individuals with multiple-domain MCI reported shorter sleep duration and lower overall sleep quality.

Brain metabolism and cerebrospinal fluid biomarkers profile of non-amnestic mild cognitive impairment in comparison to amnestic mild cognitive impairment and normal older subjects.

INTRODUCTION: Mild cognitive impairment (MCI) is classically considered a transitional stage between normal aging and dementia. Non-amnestic MCI (naMCI) patients, however, typically demonstrate cognitive deficits other than memory decline. Furthermore, as a group, naMCI have a lower rate of an eventual dementia diagnosis as compared to amnestic subtypes of MCI (aMCI). Unfortunately, studies investigating biomarker profiles of naMCI are scarce. The study objective was to investigate the regional brain glucose metabolism (rBGM) with [18F]FDG-PET and cerebrospinal fluid (CSF) biomarkers in subjects with naMCI as compared to a control group (CG) and aMCI subjects. METHODS: Ninety-five patients were included in three different groups: naMCI (N = 32), aMCI (N = 33) and CG (N = 30). Patients underwent brain MRI and [18F]FDG-PET. A subsample (naMCI = 26, aMCI = 28) also had an assessment of amyloid-ß, tau, and phosphorylated tau levels in the CSF. RESULTS: Both MCI groups had lower rBGM in relation to the CG in the precuneus. Subjects with naMCI showed decreased right prefrontal metabolism as well as higher levels of CSF amyloid-ß relative to aMCI subjects. CONCLUSION: While amnestic MCI subjects showed a biomarker profile classically related to MCI due to Alzheimer's disease, naMCI patients illustrated a decrease in both prefrontal hypometabolism and higher CSF amyloid-ß levels relative to the aMCI group. These biomarker findings indicate that naMCI is probably a heterogeneous group with similar precuneus hypometabolism compared to aMCI, but additional frontal hypometabolism and less amyloid-ß deposition in the brain. Clinical follow-up and reappraisal of biomarkers of the naMCI group is needed to determine the outcome and probable etiological diagnosis.

Analysis of the posterior cingulate cortex with [18F]FDG-PET and Naa/mI in mild cognitive impairment and Alzheimer's disease: Correlations and differences between the two methods.

Reduction of regional brain glucose metabolism (rBGM) measured by [18F]FDG-PET in the posterior cingulate cortex (PCC) has been associated with a higher conversion rate from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Magnetic Resonance Spectroscopy (MRS) is a potential biomarker that has disclosed Naa/mI reductions within the PCC in both MCI and AD. Studies investigating the relationships between the two modalities are scarce. OBJECTIVE: To evaluate differences and possible correlations between the findings of rBGM and NAA/mI in the PCC of individuals with AD, MCI and of cognitively normal volunteers. METHODS: Patients diagnosed with AD (N=32) or MCI (N=27) and cognitively normal older adults (CG, N=28), were submitted to [18F]FDG-PET and MRS to analyze the PCC. The two methods were compared and possible correlations between the modalities were investigated. RESULTS: The AD group exhibited rBGM reduction in the PCC when compared to the CG but not in the MCI group. MRS revealed lower NAA/mI values in the AD group compared to the CG but not in the MCI group. A positive correlation between rBGM and NAA/mI in the PCC was found. NAA/mI reduction in the PCC differentiated AD patients from control subjects with an area under the ROC curve of 0.70, while [18F]FDG-PET yielded a value of 0.93. CONCLUSION: rBGM and Naa/mI in the PCC were positively correlated in patients with MCI and AD. [18F]FDG-PET had greater accuracy than MRS for discriminating AD patients from controls.

Redução do metabolismo cerebral regional glicolítico (MRG) medido pela PET-18FDG no giro do cíngulo posterior (GCP) está relacionada a maior conversão para doença de Alzheimer (DA) em sujeitos com comprometimento cognitivo leve (CCL). Espectroscopia por ressonância magnética (MRS), um biomarcador promissor, demonstra redução de Naa/mI no GCP na DA. Raros estudos avaliam relações entre Naa/mI e MRG. OBJETIVO: Avaliar diferenças e possíveis correlações entre MRG com PET-18FDG e Naa/mI por MRS no GCP de sujeitos com DA, CCL e voluntários normais. MÉTODOS: Sujeitos com DA (N=32), CCL amnéstico (N=27) e voluntários idosos normais (GC, N=28), foram submetidos a PET-18FDG e análise de Naa/mI no GCP. A performance de ambos os métodos foi então comparada e verificou-se a existência de correlações entre os achados da PET e da MRS. RESULTADOS: Observou-se hipometabolismo glicolítico nos pacientes com DA no GCP em relação ao GC, porém não no CCL. A MRS demonstrou valores menores de Naa/mI no CP do grupo DA em relação ao GC, porém também sem diferenças entre CCL e GC. A área sob a curva ROC demonstrou valor de 0,70 para MRS e 0,93 para o MRG no GCP para diferenciar DA do GC. Houve correlação positiva entre o MRG e o Naa/mI no GCP. CONCLUSÃO: Os valores de metabolismo de glicose à PET e de Naa/mI à MRS no giro do cíngulo posterior apresentaram correlação positiva estatisticamente significante na presente amostra. Houve ainda superioridade da PET-18FDG para diferenciar DA do GC.

Topography of 11C-Pittsburgh compound B uptake in Alzheimer's disease: a voxel-based investigation of cortical and white matter regions

Objective: To compare results of positron emission tomography (PET) with carbon-11-labeled Pittsburgh compound B (11C-PIB) obtained with cerebellar or global brain uptake for voxel intensity normalization, describe the cortical sites with highest tracer uptake in subjects with mild Alzheimer's disease (AD), and explore possible group differences in 11C-PIB binding to white matter. Methods: 11C-PIB PET scans were acquired from subjects with AD (n=17) and healthy elderly controls (n=19). Voxel-based analysis was performed with statistical parametric mapping (SPM). Results: Cerebellar normalization showed higher 11C-PIB uptake in the AD group relative to controls throughout the cerebral cortex, involving the lateral temporal, orbitofrontal, and superior parietal cortices. With global uptake normalization, greatest cortical binding was detected in the orbitofrontal cortex; decreased 11C-PIB uptake in white matter was found in the posterior hippocampal region, corpus callosum, pons, and internal capsule. Conclusion: The present case-control voxelwise 11C-PIB PET comparison highlighted the regional distribution of amyloid deposition in the cerebral cortex of mildly demented AD patients. Tracer uptake was highest in the orbitofrontal cortex. Decreased 11C-PIB uptake in white-matter regions in this patient population may be a marker of white-matter damage in AD.

Consistency of FDG-PET accuracy and cost-effectiveness in initial staging of patients with Hodgkin lymphoma across jurisdictions.

INTRODUCTION: Two hundred ten patients with newly diagnosed Hodgkin's lymphoma (HL) were consecutively enrolled in this prospective trial to evaluate the cost-effectiveness of fluorine-18 ((18)F)-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) scan in initial staging of patients with HL. METHODS: All 210 patients were staged with conventional clinical staging (CCS) methods, including computed tomography (CT), bone marrow biopsy (BMB), and laboratory tests. Patients were also submitted to metabolic staging (MS) with whole-body FDG-PET scan before the beginning of treatment. A standard of reference for staging was determined with all staging procedures, histologic examination, and follow-up examinations. The accuracy of the CCS was compared with the MS. Local unit costs of procedures and tests were evaluated. Incremental cost-effectiveness ratio (ICER) was calculated for both strategies. RESULTS: In the 210 patients with HL, the sensitivity for initial staging of FDG-PET was higher than that of CT and BMB in initial staging (97.9% vs. 87.3%; P < .001 and 94.2% vs. 71.4%, P < 0.003, respectively). The incorporation of FDG-PET in the staging procedure upstaged disease in 50 (24%) patients and downstaged disease in 17 (8%) patients. Changes in treatment would be seen in 32 (15%) patients. Cumulative cost for staging procedures was $3751/patient for CCS compared to $5081 for CCS + PET and $4588 for PET/CT. The ICER of PET/CT strategy was $16,215 per patient with modified treatment. PET/CT costs at the beginning and end of treatment would increase total costs of HL staging and first-line treatment by only 2%. CONCLUSION: FDG-PET is more accurate than CT and BMB in HL staging. Given observed probabilities, FDG-PET is highly cost-effective in the public health care program in Brazil.