Extrastriatal dopamine D2/3 receptor binding, functional connectivity, and autism socio-communicational deficits: a PET and fMRI study.

The social motivation hypothesis of autism proposes that social communication symptoms in autism-spectrum disorder (ASD) stem from atypical social attention and reward networks, where dopamine acts as a crucial mediator. However, despite evidence indicating that individuals with ASD show atypical activation in extrastriatal regions while processing reward and social stimuli, no previous studies have measured extrastriatal dopamine D2/3 receptor (D2/3R) availability in ASD. Here, we investigated extrastriatal D2/3R availability in individuals with ASD and its association with ASD social communication symptoms using positron emission tomography (PET). Moreover, we employed a whole-brain multivariate pattern analysis of resting-state functional magnetic resonance imaging (fMRI) to identify regions where functional connectivity atypically correlates with D2/3R availability depending on ASD diagnosis. Twenty-two psychotropic-free males with ASD and 24 age- and intelligence quotient-matched typically developing males underwent [11C]FLB457 PET, fMRI, and clinical symptom assessment. Participants with ASD showed lower D2/3R availability throughout the D2/3R-rich extrastriatal regions of the dopaminergic pathways. Among these, the posterior region of the thalamus, which primarily comprises the pulvinar, displayed the largest effect size for the lower D2/3R availability, which correlated with a higher score on the Social Affect domain of the Autism Diagnostic Observation Schedule-2 in participants with ASD. Moreover, lower D2/3R availability was correlated with lower functional connectivity of the thalamus-superior temporal sulcus and cerebellum-medial occipital cortex, specifically in individuals with ASD. The current findings provide novel molecular evidence for the social motivation theory of autism and offer a novel therapeutic target.

Urinary fluorescent metabolite O-aminohippuric acid is a useful biomarker for lung cancer detection.

INTRODUCTION: Urine contains diagnostically important metabolites that can act as natural fluorophores. However, whether these fluorescent metabolites can be used in lung cancer diagnosis is unknown. OBJECTIVES: This study was conducted to determine whether fluorescent urinary metabolites could be useful biomarkers for lung cancer detection. METHODS: A total of 46 lung cancer patients and 185 volunteers without cancer were evaluated between November 2013 and November 2014. Samples of the first urine of the day were collected from lung cancer patients and diagnosed at the Hamamatsu University School of Medicine and the Hamamatsu Medical Center prior to cancer treatment, and from volunteers without cancer at the Hamamatsu Medical Imaging Center. Fluorescent urinary metabolites were screened by high-performance liquid chromatography and select effective fluorescent substances for distinguishing cancer from non-cancer status. RESULTS: The fraction of patients at each stage of cancer severity were: 41.3% stage I, 8.7% stage II, 19.6% stage III, and 30.4% stage IV. A robust predictive biomarker for lung cancer was selected by the multivariate logistic analysis of fluorescent metabolites and identified to be O-aminohippuric acid (OAH). The area under the curve (AUC) data for OAH was 0.837 (95% CI 0.769-0.898, P < 0.001). CONCLUSION: We identified a fluorescent urinary metabolite that can predict lung cancer. OAH exceeds the AUC (0.817) of lung cancer detection by AminoIndex® cancer screening, can be analyzed non-invasively without additional sample processing, and may be a valuable addition to existing lung cancer prediction models.

[Impact of point spread function correction in standardized uptake value quantitation for positron emission tomography images: a study based on phantom experiments and clinical images].

While point spread function (PSF)-based positron emission tomography (PET) reconstruction effectively improves the spatial resolution and image quality of PET, it may damage its quantitative properties by producing edge artifacts, or Gibbs artifacts, which appear to cause overestimation of regional radioactivity concentration. In this report, we investigated how edge artifacts produce negative effects on the quantitative properties of PET. Experiments with a National Electrical Manufacturers Association (NEMA) phantom, containing radioactive spheres of a variety of sizes and background filled with cold air or water, or radioactive solutions, showed that profiles modified by edge artifacts were reproducible regardless of background µ values, and the effects of edge artifacts increased with increasing sphere-to-background radioactivity concentration ratio (S/B ratio). Profiles were also affected by edge artifacts in complex fashion in response to variable combinations of sphere sizes and S/B ratios; and central single-peak overestimation up to 50% was occasionally noted in relatively small spheres with high S/B ratios. Effects of edge artifacts were obscured in spheres with low S/B ratios. In patient images with a variety of focal lesions, areas of higher radioactivity accumulation were generally more enhanced by edge artifacts, but the effects were variable depending on the size of and accumulation in the lesion. PET images generated using PSF-based reconstruction are therefore not appropriate for the evaluation of SUV.

Factors associated with fluorine-18-fluorodeoxyglucose uptake in benign thyroid nodules.

Thyroid nodules that exhibit focal uptake of fluorine-18 ((18)F)-fluorodeoxyglucose (FDG) are relatively frequent. Although the clinical features and associated mechanisms of FDG-avid lesions in both thyroid cancer and cytologically indeterminate nodules have been extensively studied, not much information is available on benign nodules. Therefore, in this retrospective study, the clinical, serological, and sonographic features of 15 benign FDG-avid nodules were compared with those of 17 non-avid lesions. Univariate analysis indicated that the FDG-positive and -negative nodules were similar with regard to age, gender, thyroid stimulating hormone (TSH), anti-thyroglobulin antibodies, tumor size, 4 B-mode sonographic findings (i.e., shape, margin, texture, and echo level), and/or elasticity. The presence of intranodular blood flow and the absence of a cystic component were associated with a greater possibility of positive FDG uptake. Multivariate analysis showed that vascularity was the only independent factor predicting FDG uptake. Across a wide range of tumor types, the extent of FDG uptake is positively correlated with tumor perfusion; this observation is consistent with the results of this study, which shows that FDG uptake in benign thyroid nodules is associated with increased vascularity.

Lower Availability of Mitochondrial Complex I in Anterior Cingulate Cortex in Autism: A Positron Emission Tomography Study.

OBJECTIVE: Mitochondrial dysfunction has been implicated in the pathophysiology of autism spectrum disorder (ASD) in previous studies of postmortem brain or peripheral samples. The authors investigated whether and where mitochondrial dysfunction occurs in the living brains of individuals with ASD and to identify the clinical correlates of detected mitochondrial dysfunction. METHODS: This case-control study used positron emission tomography (PET) with 2-tert-butyl-4-chloro-5-{6-[2-(2-[18F]fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([18F]BCPP-EF), a radioligand that binds to the mitochondrial electron transport chain complex I, to examine the topographical distribution of mitochondrial dysfunction in living brains of individuals with ASD. Twenty-three adult males with high-functioning ASD, with no psychiatric comorbidities and free of psychotropic medication, and 24 typically developed males with no psychiatric diagnoses, matched with the ASD group on age, parental socioeconomic background, and IQ, underwent [18F]BCPP-EF PET measurements. Individuals with mitochondrial disease were excluded by clinical evaluation and blood tests for abnormalities in lactate and pyruvate levels. RESULTS: Among the brain regions in which mitochondrial dysfunction has been reported in postmortem studies of autistic brains, participants with ASD had significantly decreased [18F]BCPP-EF availability specifically in the anterior cingulate cortex compared with typically developed participants. The regional specificity was revealed by a significant interaction between diagnosis and brain regions. Moreover, the lower [18F]BCPP-EF availability in the anterior cingulate cortex was significantly correlated with the more severe ASD core symptom of social communication deficits. CONCLUSIONS: This study provides direct evidence to link in vivo brain mitochondrial dysfunction with ASD pathophysiology and its communicational deficits. The findings support the possibility that mitochondrial electron transport chain complex I is a novel therapeutic target for ASD core symptoms.

Deep-learning prediction of amyloid deposition from early-phase amyloid positron emission tomography imaging.

OBJECTIVE: While the use of biomarkers for the detection of early and preclinical Alzheimer's Disease has become essential, the need to wait for over an hour after injection to obtain sufficient image quality can be challenging for patients with suspected dementia and their caregivers. This study aimed to develop an image-based deep-learning technique to generate delayed uptake patterns of amyloid positron emission tomography (PET) images using only early-phase images obtained from 0-20 min after radiotracer injection. METHODS: We prepared pairs of early and delayed [11C]PiB dynamic images from 253 patients (cognitively normal n = 32, fronto-temporal dementia n = 39, mild cognitive impairment n = 19, Alzheimer's disease n = 163) as a training dataset. The neural network was trained with the early images as the input, and the output was the corresponding delayed image. A U-net convolutional neural network (CNN) and a conditional generative adversarial network (C-GAN) were used for the deep-learning architecture and the data augmentation methods, respectively. Then, an independent test data set consisting of early-phase amyloid PET images (n = 19) was used to generate corresponding delayed images using the trained network. Two nuclear medicine physicians interpreted the actual delayed images and predicted delayed images for amyloid positivity. In addition, the concordance of the actual delayed and predicted delayed images was assessed statistically. RESULTS: The concordance of amyloid positivity between the actual versus AI-predicted delayed images was 79%(κ = 0.60) and 79% (κ = 0.59) for each physician, respectively. In addition, the physicians' agreement rate was at 89% (κ = 0.79) when the same image was interpreted. And, the actual versus AI-predicted delayed images were not readily distinguishable (correct answer rate, 55% and 47% for each physician, respectively). The statistical comparison of the actual versus the predicted delated images indicated that the peak signal-to-noise ratio (PSNR) was 21.8 dB ± 2.2 dB, and the structural similarity index (SSIM) was 0.45 ± 0.04. CONCLUSION: This study demonstrates the feasibility of an image-based deep-learning framework to predict delayed patterns of Amyloid PET uptake using only the early phase images. This AI-based image generation method has the potential to reduce scan time for amyloid PET and increase the patient throughput, without sacrificing diagnostic accuracy for amyloid positivity.

Prospective Employer-Initiated Whole-Body Cancer Screening-Costs and Outcomes of a Cancer Screening Program in Japan.

PURPOSES: To determine cancer detection and mortality and its costs associated with employee-initiated, prospective whole-body cancer screening program in an engineering company in Hamamatsu, Japan. MATERIALS AND METHODS: The program includes whole-body fluorine-18-2-fluoro-2-deoxy-D-glucose PET/CT, brain and pelvis MR, and abdominal ultrasound, offered every 2 years five consecutive times. Employees are free to opt in or opt out anytime. The subjects were divided into the full (five consecutive screenings), partial (more than once and less than five), and no participation groups. The rate ratio of cancer detection rate and cancer-related mortality and cancer-related costs of care were measured. All employees also received other annual health screenings, including chest radiograph or upper gastrointestinal study. RESULTS: Among 1,213 subjects, 543 employees were under full participation, 318 were under partial participation, and 352 were under no participation. In all, 26, 9, and 19 cancers were detected from the full participation, partial participation, and nonparticipation groups, respectively. No statistical significance was observed in the cancer detection rate ratio. The rate ratio of cancer-related deaths was 0.11 (0.01-0.90) for the full participation group compared with the nonparticipation group, and the difference was statistically significant. The cost of cancer-related care was highest among the nonparticipation group; however, the difference was not statistically significant (P = .108). CONCLUSION: Whole-body cancer screening can successfully reduce cancer-related mortality and costs of cancer-related care. The cancer detection rate was not significantly improved because of broad implementation of additional annual health screenings offered to all employees at no cost, resulting in the high baseline cancer detection rate.

High incidence of thyroid cancer in focal thyroid incidentaloma detected by 18F-fluorodeoxyglucose [corrected] positron emission tomography in relatively young healthy subjects: results of 3-year follow-up.

As 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is becoming a common imaging modality, the number of thyroid incidentalomas identified by FDG-PET (PET incidentaloma) is increasing. The purpose of this study was to elucidate the risk of cancer in focal thyroid PET incidentaloma in healthy subjects of relatively younger age as well as the usefulness of repeated FDG-PET. The study was conducted with an observation period of three years. A total of 1,501 healthy volunteers (mean age, 43.5+/-9.7 years) underwent the first FDG-PET from August 2003 to July 2004. When focal thyroid PET incidentaloma was found, further diagnostic examination was conducted. When thyroid cancer was suspected, surgical resection was performed with the patient' s agreement. Patients with PET incidentaloma without surgery were offered annual US and FDG-PET and finally FNAB was performed in the fourth year. Focal thyroid PET incidentaloma was observed in 20 subjects. The final diagnoses in 20 subjects were malignant in 11 (ten papillary thyroid carcinoma (PTC) and one thyroid carcinoma showing thymus-like differentiation), indeterminate in one, and benign in eight subjects. Seven patients not treated surgically at the first examination had annual FDG-PET. One patient with PTC showed increasing SUVmax, but another with a benign nodule exhibited a similar increase. Others (one with PTC, one with an indeterminate nodule, and three with benign nodules) exhibited negligible SUVmax changes. When closely examined, focal thyroid PET incidentaloma in relatively young healthy adults has a high probability of malignancy. Repeated FDG-PET to follow up patients with thyroid nodules is ineffective.

Ten-year prospective evaluation of whole-body cancer screening with multiple modalities including [18F]fluorodeoxyglucose positron emission tomography in a healthy population.

PURPOSE: To prospectively evaluate the value of whole-body cancer screening with multiple modalities including FDG-PET in a healthy population. METHODS: The study was conducted in 1197 healthy individuals aged ≥ 35 years at enrollment between August 2003 and July 2004. All participants were scheduled to receive annual whole-body cancer screening five times (screening period) with subsequent long-term follow-up (follow-up period). The endpoints of the study were definitive cancer diagnosis, cancer-related death, and all-cause death. RESULTS: The follow-up rate was 99.8% for the screening period and 96.2% for the follow-up period. Forty-five cancers were confirmed during the screening period (August 2003 to July 2009), and 37 of the 45 were detected by the screening. Fourteen of the 45 were PET positive. Sixteen, 5, 4, 9 and 11 cancers were confirmed after the first, the second, the third, the fourth, and the fifth (took 2 years) screening, respectively. Eight participants died, of whom five died of cancer. The rate of cancer incidence (per 100,000) of 628.7 (95% confidence interval [CI] 445.0-812.4) was significantly high, and the rates of cancer mortality and all-cause mortality of 69.9 (95% CI 8.6-131.1) and 111.8 (95% CI 34.3-189.2), respectively, were significantly low, compared with the corresponding rates of 379.3, 138.2 and 354.2, respectively, in the age-rank- and sex-matched general population. During the follow-up period (August 2009 to July 2013), 37 cancers were confirmed and 30 of the 37 were detected. Seven participants died, of whom three died of cancer. The rate of cancer incidence was 809.6 (95% CI 548.7-1070.5). The rates of cancer mortality and all-cause mortality of 65.6 (95% CI 0-139.9) and 153.2 (95% CI 39.7-266.6), respectively, were significantly low compared with 190.1 and 462.3, respectively, in the general population. CONCLUSION: Cancer detection by PET alone was limited. While the high cancer incidence was attributed to the extensive screening, the low cancer and all-cause mortality may indicate the potential value of this type of cancer screening. Cancer incidence increases with aging and it has been shown that continuous screening may reduce the risk caused by the cancer progression.

The frequency of the plicae palmatae in the uterine cervix on MR imaging.

BACKGROUND: The plicae palmatae is a developmental remnant of the Müllerian ductal fusion, which is demonstrated as a ridge of low intensity in the cervical canal on axial T2-weighted MR images. The identification of the plicae palmatae on MR imaging is beneficial for avoiding misinterpretation of this finding as anomalous uterine septum. The current study is performed to investigate the frequency of this finding and its variation among different age groups. METHODS: Axial T2-weighted images in 433 subjects were evaluated regarding the presence of the plicae palmatae and uterine anomaly. RESULTS: The frequency of the plicae palmatae was 47.5-53.2% in the third to fifth decade groups, but it was significantly lower in the sixth decade group (24.8%) than in the fifth decade group (53.2%). In three subjects with uterine anomalies, the plicae palmatae was recognized in a bicornuate uterus with single cervix, whereas it was not identified in unicornuate uterus and bicornuate uterus with duplicated cervices. CONCLUSION: The plicae palmatae is commonly encountered in routine MR images of normal uterus, especially in reproductive-aged women.

[Assessment of diagnostic criteria for FDG-PET cancer screening program according to the interpretation of FDG-PET and combined examination].

OBJECTIVE: The aim of this study is to establish the diagnostic criteria for FDG-PET cancer screening program of four kinds of organ (breast, thyroid, lung and colon/rectum) according to the interpretation of FDG-PET cancer screening program of the case with proved clinical outcome. METHODS: Among FDG-PET cancer screening examinations performed in two PET centers during 2003 to 2006, two hundreds of examinations with proved clinical outcome were evaluated. Interpretation of breast ultrasonography, thyroid ultrasonography, chest CT and fecal occult blood testing, which were regarded as combined examinations, were performed together with the interpretation of FDG-PET images. RESULTS: As a result of the interpretation, localized FDG accumulating site in all four organs should be recommended for further inspections. In addition, essential point for diagnosis was considered as follows; (1) check over the slight localized FDG accumulation with screening of breast region, (2) combine chest CT with FDG-PET for the evaluation of lung region and (3) check up the shift of FDG accumulation between early and delayed phase with screening of colon/rectum region. CONCLUSIONS: According to the interpretation results of this study, we establish diagnostic criteria of FDG-PET and combined examination of four kinds of organ.

Automated segmentation of 2D low-dose CT images of the psoas-major muscle using deep convolutional neural networks.

The psoas-major muscle has been reported as a predictive factor of sarcopenia. The cross-sectional area (CSA) of the psoas-major muscle in axial images has been indicated to correlate well with the whole-body skeletal muscle mass. In this study, we evaluated the segmentation accuracy of low-dose X-ray computed tomography (CT) images of the psoas-major muscle using the U-Net convolutional neural network, which is a deep-learning technique. Deep learning has been recently known to outperform conventional image-segmentation techniques. We used fivefold cross validation to validate the segmentation performance (n = 100) of the psoas-major muscle. For the intersection over union and CSA ratio, segmentation accuracies of 86.0 and 103.1%, respectively, were achieved. These results suggest that the U-Net network is competitive compared with the previous methods. Therefore, the proposed technique is useful for segmenting the psoas-major muscle even in low-dose CT images.

Incidence and characteristics of uterine leiomyomas with FDG uptake.

OBJECTIVE: Uterine leiomyomas sometimes show focal 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) images that may result in a false-positive diagnosis for malignant lesions. This study was conducted to investigate the incidence and characteristics of uterine leiomyomas that showed FDG uptake. METHODS: We reviewed FDG-PET and pelvic magnetic resonance (MR) images of 477 pre-menopausal (pre-MP, age 42.1 +/- 7.3 years) and 880 post-MP (age 59.9 +/- 6.8 years) healthy women who underwent these tests as parts of cancer screening. Of 1357, 323 underwent annual cancer screening four times, 97 did three times, 191 did twice, and the rest were screened once. Focal FDG uptake (maximal standardized uptake value > 3.0) in the pelvis was localized and characterized on co-registered PET/MR images. RESULTS: Uterine leiomyomas were found in 164 pre-MP and 338 post-MP women. FDG uptake was observed in 18 leiomyomas of 17 of the 164 (10.4%) pre-MP women and in 4 leiomyomas of 4 of the 338 (1.2%) post-MP women. The incidence was significantly higher in pre-MP women than in post-MP women (chi-square, P < 0.001). Of the 22, 13 showed signal intensity equal to or higher than that of the myometrium on T2-weighted MR images, which suggested abundant cellularity, whereas the majority of leiomyomas without FDG uptake showed low signal intensity. Of the 13 women, 12 examined more than twice showed substantial changes in the level of FDG uptake in leiomyomas each year with FDG uptake disappearing or newly appearing. These changes were observed frequently in relation with menopause or menstrual phases. CONCLUSIONS: Leiomyomas with focal FDG uptake were seen in both pre-and post-MP women with a higher incidence in pre-MP women. Abundant cellularity and hormonal dependency may explain a part of the mechanisms of FDG uptake in leiomyomas. It is important to know that the level of FDG uptake in leiomyomas can change and newly appearing FDG uptake does not necessarily mean malignant transformation.

Physiological FDG uptake in the ovaries after hysterectomy.

OBJECTIVE: It is known that focal 18F-fluorodeoxyglucose (FDG) uptake is physiologically seen in the ovaries and uterus of premenopausal women in correlation with the menstrual cycle, which may cause false-positive diagnoses on the images of FDG positron emission tomography (PET). The objective of this study was to clarify whether women of reproductive age after hysterectomy whose ovaries were preserved, also showed physiological ovarian FDG uptake. METHODS: We reviewed 26 women after hysterectomy (age 51.1 +/- 5.0 years), who underwent annual cancer screening, including FDG-PET and pelvic magnetic resonance (MR) imaging, three times. RESULTS: Seven women (age 45.9 +/- 5.8 years, range 34-52 years) had at least one ovary, showing changes in its appearance including the size and number of follicles on MR images each year, which suggested that the ovary was functioning. Four of the seven women showed focal FDG uptake (standardized uptake value 4.2 +/- 1.1) that corresponded to the normal ovaries on five PET examinations. Another group of 19 women (age 53.1 +/- 3.1 years, range 47-59 years) who had small ovaries without changes on MR images each year did not show FDG uptake in the ovaries. CONCLUSIONS: Physiological FDG uptake observed in the ovaries of women of reproductive age even after hysterectomy is reasonably common. As it is not easy to determine the hormonal cycle in these women, it is essential to correlate focal FDG uptake in the pelvis with anatomical and morphological findings on MR images to avoid false-positive diagnoses.

Performance profile of FDG-PET and PET/CT for cancer screening on the basis of a Japanese Nationwide Survey.

OBJECTIVE: The aim of this study is to survey the situation of (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) cancer screening in Japan and to describe its performance profile. METHODS: "FDG-PET for cancer screening" was defined as FDG-PET or positron emission tomography and computed tomography (PET/CT) scan with or without other tests performed for cancer screening of healthy subjects. We sent questionnaires regarding FDG-PET cancer screening to 99 facilities in which FDG-PET tests were performed during the fiscal year 2005. Replies were obtained from 68 of the 99 facilities, of which 46 facilities performed FDG-PET cancer screening. The total number of subjects who underwent FDG-PET cancer screening was 50 558. From 38 of 46 facilities, reliable results of thorough examinations were obtained for the subjects who were positive by FDG-PET and/or one or more of the combined screening tests was performed and were referred for further evaluation. The total number of subjects in these 38 facilities amounted to 43 996. RESULTS: A total of 50,558 healthy subjects underwent FDG-PET (including PET/CT) scanning with or without other tests for cancer screening in 46 PET centers during the fiscal year of 2005 in Japan. Thorough examination was indicated for 9.8% of the cases as a result of positive findings suggesting possible cancer. On analyzing 43 996 cases from 38 PET centers from which detailed information was obtained, 500 cases of cancers (1.14%) were found, of which 0.90% were PET positive and 0.24% were PET negative, resulting in the relative sensitivity of PET being 79.0%. Cancers of the thyroid, colon/rectum, lung, and breast were most frequently found (107, 102, 79, and 35 cases, respectively) with high PET sensitivity (88%, 90%, 80%, and 92%). PET showed an overall positive predictive value of 29.0%. PET/CT had a better detection rate, sensitivity, and positive predictive value than dedicated PET (P < 0.01). CONCLUSIONS: We were able to clarify the performance profile of "FDG-PET for cancer screening" on the basis of a Japanese nationwide survey. The number of facilities possessing PET is increasing steadily, highlighting the necessity of evaluating the usefulness of "FDG-PET cancer screening" as soon as possible by undertaking long-term investigations of large series of subjects.

[Performance profile of FDG-PET and PET/CT for cancer screening based on a Japanese nationwide survey].

A total of 50,558 healthy subjects underwent an FDG-PET (including PET/CT) scan with or without combination of other tests for cancer screening in 46 PET centers during fiscal year of 2005 in Japan. Thorough examination was indicated for 9.8% of the cases due to positive findings suggesting possible cancer. On analyzing 43,996 cases from 38 PET centers, where detailed information was obtained, 500 cases of cancers (1.14%) were found, of which 0.90% was PET positive and 0.24% was PET negative, resulting in the relative sensitivity of PET being 79.0%. Cancers of thyroid, colon/rectum, lung and breast were most frequently found (107, 102, 79, 35 cases, respectively) with high PET sensitivity (88%, 90%, 80%, 92%). PET showed an overall positive predictive value of 29.0%. PET/CT had better detection rate, sensitivity, and positive predictive value than dedicated PET (p<0.01).

Age-Related Sex-Specific Changes in Brain Metabolism and Morphology.

UNLABELLED: With a large database, we aimed to evaluate sex-specific distinctive changes in brain glucose metabolism and morphology during normal aging using MRI and (18)F-FDG PET. METHODS: A total of 963 cognitively healthy adults were included in this study. All subjects completed a medical questionnaire, took the mini-mental state examination, and underwent brain MRI and whole-body (18)F-FDG PET. The MR and PET images were statistically analyzed using 3-dimensional stereotactic surface projection. All images were corrected for whole-brain pixel value to identify the brain regions with significant changes, and regions of interest were set up with reference to Brodmann areas. We evaluated morphologic and glucose metabolic changes by cross-sectional analysis. The baseline database consisted of subjects from 30 to 40 y old, and the age-step for comparison was 5-y ranges. We also compared sex-specific differences in MR and PET images in each age group. RESULTS: Regarding age-related changes, in both sexes brain atrophy was observed in the lateral frontal and parietal regions and glucose hypometabolism in the medial frontal regions. There were significant differences in these parameters between the sexes; parallel changes in volume and metabolism were manifested in the medial frontal cortex in men and in the lateral and medial temporal cortex in women. By contrast, metabolism-dominant reductions were manifested in the lateral and medial parietal cortex in men and in the ventrolateral prefrontal cortex, including the Broca area, in women. These differences became insignificant in individuals 66 y or older. CONCLUSION: Our brain mapping study with a large number of reference human brain data demonstrated age-related parallel changes between morphology and metabolism in the medial frontal regions and sex-specific hypometabolism in the parietal (male) and ventrolateral prefrontal (female) cortices. These findings may suggest an aging vulnerability in sex-specific brain regions: the parietal cortex for visuospatial ability in men and the Broca area for speech processing in women.

Prospective comparison of 18F-FDG PET with conventional imaging modalities (MRI, CT, and 67Ga scintigraphy) in assessment of combined intraarterial chemotherapy and radiotherapy for head and neck carcinoma.

UNLABELLED: To preserve the oral organs and functions in patients with head and neck carcinoma, accurate determination of the appropriate treatment after neoadjuvant chemotherapy and radiotherapy is of critical importance. We evaluated the diagnostic accuracy of (18)F-FDG PET relative to that of other conventional imaging modalities in the assessment of therapeutic response after combined intraarterial chemotherapy and radiotherapy as an organ preservation protocol. METHODS: The study was prospectively performed on 23 consecutive patients with head and neck squamous cell carcinoma who completed the treatment regimen and underwent 2 (18)F-FDG PET studies before and after neoadjuvant chemoradiotherapy. (67)Ga scintigraphy (only before therapy) as well as MRI and CT (both before and after therapy) were also performed. All images were blindly and independently interpreted without knowledge of histologic findings. The level of confidence in image interpretation was graded by means of a 5-point rating system (0 = definitely no tumor to 4 = definite tumor). RESULTS: Before treatment, (18)F-FDG PET detected primary tumors in all 23 patients and was more sensitive (100%) than MRI (18/23; 78.3%), CT (15/22; 68.2%), and (67)Ga scintigraphy (8/20; 40%), with a confidence level of 3 or 4 as a positive tumor finding. After chemoradiotherapy, residual tumors were histologically confirmed in 4 patients (pathologic complete response rate, 19/23; 82.6%). Although posttreatment (18)F-FDG PET showed almost equal sensitivity (4/4; 100%) compared with MRI (3/3; 100%) or CT (3/4; 75%), its specificity (17/19; 89.5%) was superior to MRI (7/17, 41.2%) and to CT (10/17; 58.8%) for primary lesions. Regarding metastases to neck lymph nodes, only specificity for posttreatment images was calculated because no metastasis was confirmed in any patients after treatment. Six subjects had (18)F-FDG PET-positive lymph nodes, which had pathologically no tumor cells and suggested an inflammatory reactive change after therapy. Therefore, the specificity of posttreatment (18)F-FDG PET (17/23; 73.9%) was almost identical to that of MRI (17/20; 85%) and CT (16/21; 76.2%) for neck metastasis. With combined chemoradiotherapy monitored with (18)F-FDG PET, 8 patients avoided surgery and the remaining 15 patients underwent a reduced form of surgery. CONCLUSION: (18)F-FDG PET facilitates differentiation of residual tumors from treatment-related changes after chemoradiotherapy, which may be occasionally difficult to characterize by anatomic images. (18)F-FDG PET has a clinical impact for the management of patients with head and neck cancers after neoadjuvant chemoradiotherapy by optimizing surgical treatment for each patient and contributes to the improvement of the patient's quality of life.

Simple analytic method of 11C-flumazenil metabolite in blood.

UNLABELLED: 11C-Flumazenil ((11)C-FMZ) is useful to estimate central benzodiazepine receptors by PET. The binding potential (BP) can be calculated with dynamic PET and continual blood sampling. Because conventional metabolite analysis of plasma samples is complicated and time consuming, a simple method is required to obtain an input function. In this article, a whole blood solvent extraction method was evaluated using data of 13 subjects. METHODS: The plasma solvent extraction method was estimated in comparison with the thin-layer chromatography (TLC) method. Then, the whole blood solvent extraction method was evaluated in comparison with the plasma solvent extraction method. RESULTS: Metabolite data analyzed by the plasma extraction method were well correlated with those by the TLC method (r = 0.99). The BP was calculated using both the whole blood extraction data and the plasma extraction data. No difference was observed in all brain regions. CONCLUSION: This simple whole blood solvent extraction method can be applied to clinical BP estimation using (11)C-FMZ.

Facial recognition reactivates the primary visual cortex: an functional magnetic resonance imaging study in humans.

In order to investigate how the brain represents sensory-specific information during memory retrieval, we examined functional magnetic resonance imaging's during a face-recognition task. When compared with activation associated with viewing of novel faces, recognition of faces presented 5 min before scanning activated the primary visual cortex, consistent with the hypothesis that retrieved facial information is coded by the reactivation of the brain regions engaged during sensory perception. This reactivation was not observed 14 weeks following initial presentation of the faces despite no significant difference in recognition rate between the two intervals. This suggests that accessing of visual information during memory retrieval is associated with the primary visual cortex, and that its activation is time-dependent--probably related to the memory transformation or consolidation.