Development of lung cancer risk prediction models based on F-18 FDG PET images.

OBJECTIVE: We aimed to evaluate whether the degree of F-18 fluorodeoxyglucose (FDG) uptake in the lungs is associated with an increased risk of lung cancer and to develop lung cancer risk prediction models using metabolic parameters on F-18 FDG positron emission tomography (PET). METHODS: We retrospectively included 795 healthy individuals who underwent F-18 FDG PET/CT scans for a health check-up. Individuals who developed lung cancer within 5 years of the PET/CT scan were classified into the lung cancer group (n = 136); those who did not were classified into the control group (n = 659). The healthy individuals were then randomly assigned to either the training (n = 585) or validation sets (n = 210). Clinical factors including age, sex, body mass index (BMI), and smoking history were collected. The standardized uptake value ratio (SUVR) and metabolic heterogeneity (MH) index were obtained for the bilateral lungs. Logistic regression models including clinical factors, SUVR, and MH index were generated to quantify the probability of lung cancer development using a training set. The prediction models were validated using a validation set. RESULTS: The lung SUVR and lung MH index in the lung cancer group were significantly higher than in the control group (p < 0.001 and p < 0.001, respectively). In the combined prediction model 1, age, sex, BMI, smoking history, and lung SUVR were significantly associated with lung cancer development (age: OR 1.07, p < 0.001; male: OR 2.08, p = 0.015; BMI: OR 0.93, p = 0.057; current or past smoker: OR 5.60, p < 0.001; lung SUVR: OR 1.13, p < 0.001). In the combined prediction model 2, age, sex, BMI, smoking history, and lung MH index showed a significant association with lung cancer development (age: OR 1.06, p < 0.001; male: OR 1.87, p = 0.045; BMI: OR 0.93, p = 0.010; current or past smoker: OR 4.78, p < 0.001; lung MH index: OR 1.33, p < 0.001). In the validation data, combined prediction models 1 and 2 exhibited very good discrimination [area under the receiver operator curve (AUC): 0.867 and 0.901, respectively]. CONCLUSIONS: The metabolic parameters on F-18 FDG PET are related to an increased risk of lung cancer. Metabolic parameters can be used as biomarkers to provide information independent of the clinical parameters, related to lung cancer risk.

Prognostic value of the metabolic score obtained via [18F]FDG PET/CT and a new prognostic staging system for gastric cancer.

We developed and validated a new staging system that includes metabolic information from pretreatment [18F]Fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) for predicting disease-specific survival (DSS) in gastric cancer (GC) patients. Overall, 731 GC patients undergoing preoperative [18F]FDG PET/CT were enrolled and divided into the training (n = 543) and validation (n = 188) cohorts. A metabolic score (MS) was developed by combining the maximum standardized uptake value (SUVmax) of the primary tumor (T_SUVmax) and metastatic lymph node (N_SUVmax). A new staging system incorporating the MS and tumor-node-metastasis (TNM) stage was developed using conditional inference tree analysis. The MS was stratified as follows: score 1 (T_SUVmax ≤ 4.5 and N_SUVmax ≤ 1.9), score 2 (T_SUVmax > 4.5 and N_SUVmax ≤ 1.9), score 3 (T_SUVmax ≤ 4.5 and N_SUVmax > 1.9), and score 4 (T_SUVmax > 4.5 and N_SUVmax > 1.9) in the training cohort. The new staging system yielded five risk categories: category I (TNM I, II and MS 1), category II (TNM I, II and MS 2), category III (TNM I, II and MS ≥ 3), category IV (TNM III, IV and MS ≤ 3), and category V (TNM III, IV and MS 4) in the training cohort. DSS differed significantly between both staging systems; the new staging system showed better prognostic performance in both training and validation cohorts. The MS was an independent prognostic factor for DSS, and discriminatory power of the new staging system for DSS was better than that of the conventional TNM staging system alone.

Association between Visceral Adipose Tissue Metabolism and Alzheimer's Disease Pathology.

The visceral adipose tissue (VAT) has been recognized as an endocrine organ, and VAT dysfunction could be a risk factor for Alzheimer's disease (AD). We aimed to evaluate the association of VAT metabolism with AD pathology. This cross-sectional study included 54 older subjects with cognitive impairment who underwent 2-deoxy-2-[fluorine-18]-fluoro-D-glucose (18F-FDG) torso positron emission tomography (PET) and 18F-florbetaben brain PET. 18F-FDG uptake in VAT on 18F-FDG PET images was used as a marker of VAT metabolism, and subjects were classified into high and low VAT metabolism groups. A voxel-based analysis revealed that the high VAT metabolism group exhibited a significantly higher cerebral amyloid-ß (Aß) burden than the low VAT metabolism group. In the volume-of-interest analysis, multiple linear regression analyses with adjustment for age, sex, and white matter hyperintensity volume revealed that 18F-FDG uptake in VAT was significantly associated with the cerebral Aß burden (ß = 0.359, p = 0.007). In conclusion, VAT metabolism was associated with AD pathology in older subjects. Our findings suggest that VAT dysfunction could contribute to AD development.

Selective neurodegeneration of the hippocampus caused by chronic cerebral hypoperfusion: F-18 FDG PET study in rats.

BACKGROUND: Chronic cerebral hypoperfusion (CCH) is known to induce Alzheimer's disease (AD) pathology, but its mechanism remains unclear. The purpose of this study was to identify the cerebral regions that are affected by CCH, and to evaluate the development of AD pathology in a rat model of CCH. METHODS: A rat model of CCH was established by bilaterally ligating the common carotid arteries in adult male rats (CCH group). The identical operations were performed on sham rats without arteries ligation (control group). Regional cerebral glucose metabolism was evaluated at 1 and 3 months after bilateral CCA ligation using positron emission tomography with F-18 fluorodeoxyglucose. The expression levels of amyloid ß40 (Aß40), amyloid ß42 (Aß42), and hyperphosphorylated tau were evaluated using western blots at 3 months after the ligation. Cognitive function was evaluated using the Y-maze test at 3 months after the ligation. RESULTS: At 1 month after the ligation, cerebral glucose metabolism in the entorhinal, frontal association, motor, and somatosensory cortices were significantly decreased in the CCH group compared with those in the control group. At 3 months after the ligation, cerebral glucose metabolism was normalized in all regions except for the anterodorsal hippocampus, which was significantly decreased compared with that of the control group. The expression of Aß42 and the Aß42/40 ratio were significantly higher in the CCH group than those in the control group. The phosphorylated-tau levels of the hippocampus in the CCH group were significantly lower than those in the control group. Cognitive function was more impaired in the CCH group than that in the control group. CONCLUSION: Our findings suggest that CCH causes selective neurodegeneration of the anterodorsal hippocampus, which may be a trigger point for the development of AD pathology.

Incidence rate and factors associated with the development of secondary cancers after radioiodine therapy in differentiated thyroid cancer: a multicenter retrospective study.

PURPOSE: The objective of this study was to estimate the incidence of secondary cancers and the factors associated with their development among patients who underwent radioiodine therapy (RIT) with differentiated thyroid cancer. METHODS: We retrospectively collected medical records for patients who underwent first RIT between January 1, 2000, and December 31, 2005, from seven tertiary hospitals in South Korea after total thyroidectomy for differentiated thyroid cancer. Cancer incidence and calculated standardized rate ratio were compared with Korean cancer incidence data. The association between the development of secondary cancers and various parameters was analyzed by Cox-proportional hazard regression. RESULTS: A total of 3106 patients were included in this study. Mean age at the time of diagnosis of thyroid cancer was 45.7 ± 13.3 years old, and 2669 (85.9%) patients were female. The follow-up period was 11.9 ± 4.6 (range, 1.2-19.6) years. A total of 183 secondary cancers, which included 162 solid and 21 hematologic cancers, occurred in 173 patients (5.6%). There was no significant difference between solid cancer incidence in our study population who underwent RIT and the overall Korean population, but the incidence of hematologic cancers and total cancer in our study was significantly higher compared with that of the Korean population. A multivariate analysis identified independent prognostic factors for the development of secondary cancer including age at 1st RIT, male, and total cumulative dose over 200 mCi. CONCLUSION: We need to assess the risk benefit for patients who receive over 200 mCi of a total cumulative dose.

Cardiac Autonomic Dysfunction Is Associated with Severity of REM Sleep without Atonia in Isolated REM Sleep Behavior Disorder.

123I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy was performed to assess cardiac autonomic dysfunction and demonstrate its correlation with clinical and polysomnographic characteristics in patients with isolated rapid eye movement (REM) sleep behavior disorder. All subjects including 39 patients with isolated REM sleep behavior disorder and 17 healthy controls underwent MIBG cardiac scintigraphy for cardiac autonomic dysfunction assessment. The isolated REM sleep behavior disorder was confirmed by in-lab overnight polysomnography. A receiver operating curve was constructed to determine the cut-off value of the early and delayed heart-to-mediastinum ratio in patients with isolated REM sleep behavior disorder. Based on each cut-off value, a comparison analysis of REM sleep without atonia was performed by dividing isolated REM sleep behavior disorder patients into two groups. MIBG uptake below the cut-off value was associated with higher REM sleep without atonia. The lower heart-to-mediastinum ratio had significantly higher REM sleep without atonia (%), both with cut-off values of early (11.0 ± 5.6 vs. 29.3 ± 23.2%, p = 0.018) and delayed heart-to-mediastinum ratio (9.1 ± 4.3 vs. 30.0 ± 22.9%, p = 0.011). These findings indicate that reduced MIBG uptake is associated with higher REM sleep without atonia in isolated REM sleep behavior disorder.

Usefulness of cyclic thermal therapy and red blood cell scintigraphy in patients with chemotherapy-induced peripheral neuropathy.

BACKGROUND: Pharmacological and non-pharmacological therapies have been used to treat patients with chemotherapy-induced peripheral neuropathy (CIPN). However, the effect of therapies in cancer patients has yet to be investigated comprehensively. We hypothesized that cyclic thermal therapy would improve blood flow and microcirculation and improve the symptoms driven by CIPN. METHODS: The criteria of assessment were blood volume in region of interest (ROI) in the images, and European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 questionnaire scores. The blood volume was quantified by using red blood cell (RBC) scintigraphy. All patients were treated 10 times during 10 days. The thermal stimulations, between 15° and 41°, were repeatedly delivered to the patient's hands. RESULTS: The total score of the questionnaires, the score of questions related to the upper limbs, the score of questions closely related to the upper limbs, and the score excluding the upper limbs questions was decreased. The blood volume was decreased, and the variance of blood volume was decreased. During cooling stimulation, the blood volume was decreased, and its variance was decreased. During warming stimulation, the blood volume was decreased, and its variance was decreased. CONCLUSIONS: We suggest that cyclic thermal therapy is useful to alleviate CIPN symptoms by blood circulation improvement. RBC scintigraphy can provide the quantitative information on blood volume under certain conditions such as stress, as well as rest, in peripheral tissue.

Prognostic value of metabolic parameters on 18F-fluorodeoxyglucose positron tomography/computed tomography in classical rectal adenocarcinoma.

We aimed to investigate the prognostic value of the metabolic parameters of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in classical rectal adenocarcinoma (CRAC). We retrospectively reviewed 149 patients with CRAC who underwent preoperative 18F-FDG PET/CT at initial diagnosis followed by curative surgical resection. 18F-FDG PET/CT metabolic parameters including maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) for disease-free survival (DFS) and overall survival (OS) were evaluated for prognostic significance by univariate and multivariate analyses, along with conventional risk factors including pathologic T (pT) stage, lymph node (LN) metastasis, lymphovascular invasion (LVI), perineural invasion (PNI), and preoperative carcinoembryonic antigen (CEA) level. On univariate analysis, high pT stage, positive LN metastasis, LVI, PNI, MTV, and TLG were significant prognostic factors affecting DFS (all P < 0.05), while CEA level, high pT stage, positive LN metastasis, LVI, PNI, MTV, and TLG affected OS (all P < 0.05). On multivariate analysis, positive LN metastasis, LVI, MTV, and TLG were independent prognostic factors affecting DFS (all P < 0.05), while CEA level, positive LN metastasis, and MTV affected OS (all P < 0.05). Thus, the volume-based metabolic parameters from preoperative 18F-FDG PET/CT scans are independent prognostic factors in patients with CRAC.

Early-Phase SPECT/CT for Diagnosing Osteomyelitis: A Retrospective Pilot Study.

OBJECTIVE: The aim of this pilot study was to investigate the potential of early-phase single-photon emission computed tomography (SPECT)/computed tomography (CT) using technetium-99m methyl diphosphonate (99mTc-MDP) for diagnosing osteomyelitis (OM). MATERIALS AND METHODS: Twenty-one patients with suspected OM were enrolled retrospectively. Three-phase bone scan (TPBS), early-phase SPECT/CT (immediately after blood pool planar imaging), and delayed-phase SPECT/CT (immediately after delayed planar imaging) were performed. The final diagnoses were established through surgery or clinical follow-up for over 6 months. We compared three diagnostic criteria based on (I) TPBS alone, (II) combined TPBS and delayed-phase SPECT/CT, and (III) early-phase SPECT/CT alone. RESULTS: OM was diagnosed in 11 of 21 patients (nine surgically and two clinically). Of the 11 OM patients, criterion-I, criterion-II, and criterion-III were positive in six, seven, and 10 patients, respectively. Of the 10 non-OM patients, criterion-I, criterion-II, and criterion-III were negative in five, five, and seven patients, respectively. The sensitivity/specificity/accuracy of criterion-I, criterion-II, and criterion-III for diagnosing OM were 54.5%/50.0%/55.0%, 63.6%/50.0%/57.1%, and 90.9%/70.0%/87.5%, respectively. CONCLUSION: This pilot study demonstrated the potential of using the early-phase SPECT/CT to diagnose OM. Based on the results, prospective studies with a larger sample size should be conducted to confirm the efficacy of early-phase SPECT/CT.

Comparison of Image Quality and Semi-quantitative Measurements with Digital PET/CT and Standard PET/CT from Different Vendors.

PURPOSE: This study aimed to evaluate the concordance and equivalence of results between the newly acquired digital PET/CT(dPET) and the standard PET/CT (sPET) to investigate possible differences in visual and semi-quantitative analyses. METHODS: A total of 30 participants were enrolled and underwent a single 18F-FDG injection followed by dual PET/CT scans, by a dPET scan, and immediately after by the sPET scan or vice versa. Two readers reviewed overall image quality using a 5-point scale and counted the number of suggestive 18F-FDG avid lesions. The SUV values were measured in the background organs and in hypermetabolic target lesions. Additionally, we objectively evaluated image quality using the liver signal-to-noise ratio (SNR). RESULTS: The dPET identified 4 additional 18F-FDG avid lesions in 3 of 30 participants with improved visual image quality. The standard deviations of SUV of the background organs were significantly lower with DigitalPET than with sPET, and dPET could acquire images with better SNR (11.13 ± 2.01 vs. 8.71 ± 1.32, P < 0.001). The reliability of SUV values between scanners showed excellent agreement. Bland-Altman plot analysis of 81 lesions showed an acceptable agreement between scanners for most of the SUVmax and SUVpeak values. No relationship between the SUV values and time delays of dual PET/CT acquisition was found. CONCLUSIONS: The dPET provides improved image quality and lesion detectability than the sPET. The semi-quantitative values of the two PET/CT systems of different vendors are comparable. This pilot study will be an important basis for possible interchangeable use of either system in clinical practice.

Prognostic Value of Restaging F-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography to Predict 3-Year Post-Recurrence Survival in Patients with Recurrent Gastric Cancer after Curative Resection.

OBJECTIVE: The aim of this study was to investigate the prognostic value of the maximum standardized uptake value (SUVmax) measured while restaging with F-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) to predict the 3-year post-recurrence survival (PRS) in patients with recurrent gastric cancer after curative surgical resection. MATERIALS AND METHODS: In total, 47 patients with recurrent gastric cancer after curative resection who underwent restaging with 18F-FDG PET/CT were included. For the semiquantitative analysis, SUVmax was measured over the visually discernable 18F-FDG-avid recurrent lesions. Cox proportional-hazards regression models were used to predict the 3-year PRS. Differences in 3-year PRS were assessed with the Kaplan-Meier analysis. RESULTS: Thirty-nine of the 47 patients (83%) expired within 3 years after recurrence in the median follow-up period of 30.3 months. In the multivariate analysis, SUVmax (p = 0.012), weight loss (p = 0.025), and neutrophil count (p = 0.006) were significant prognostic factors for 3-year PRS. The Kaplan-Meier curves demonstrated significantly poor 3-year PRS in patients with SUVmax > 5.1 than in those with SUVmax ≤ 5.1 (3-year PRS rate, 3.5% vs. 38.9%, p < 0.001). CONCLUSION: High SUVmax on restaging with 18F-FDG PET/CT is a poor prognostic factor for 3-year PRS. It may strengthen the role of 18F-FDG PET/CT in further stratifying the prognosis of recurrent gastric cancer.

Relationship Between Thyroid Hormone Levels and the Pathology of Alzheimer's Disease in Euthyroid Subjects.

Background: Although several studies have reported an association between thyroid dysfunction and Alzheimer's disease (AD), the effect of mild thyroid dysfunction within the normal range of thyrotropin (TSH) on the development of AD remains unclear. The aim of this study was to evaluate the association between thyroid hormones and the pathology of AD in euthyroid subjects. Methods: Sixty-nine subjects with a TSH level between 0.5 and 4.5 µIU/L who underwent 18F-florbetaben positron emission tomography were included in this prospective cross-sectional study. The levels of serum free thyroxine (fT4) and TSH were quantified using radioimmunoassay. Neuropsychological tests were performed to assess cognitive function. Differences in cerebral amyloid-ß (Aß) burden were compared between high-normal TSH (TSH ≥2.5 µIU/mL) and low-normal TSH (TSH <2.5 µIU/mL) groups. Multiple linear regression analyses, adjusted for age, sex, education level, and Neuropsychiatric Inventory scores, were performed to evaluate relationships between thyroid hormone levels and both cerebral Aß burden and cognitive function. Results: The cerebral Aß burden in the high-normal TSH group was significantly higher than in the low-normal TSH group (1.53 ± 0.31 vs. 1.35 ± 0.22, p = 0.009). The fT4 levels were negatively correlated with cerebral Aß burden (ß = -0.240, p = 0.035), and TSH levels were positively correlated with cerebral Aß burden (ß = 0.267, p = 0.020). The fT4 level was also positively associated with cognitive function, as inferred from neuropsychological test scores. Conclusions: Thyroid hormone concentrations were associated with AD pathology in euthyroid subjects. Our findings suggest that AD is likely to occur even in individuals with high-normal TSH levels.

Clinicopathologic risk factors of radioactive iodine therapy based on response assessment in patients with differentiated thyroid cancer: a multicenter retrospective cohort study.

PURPOSE: We investigated whether predictive clinicopathologic factors can be affected by different response criteria and how the clinical usefulness of radioactive iodine (RAI) therapy should be evaluated considering variable factors in patients with differentiated thyroid carcinoma (DTC). METHODS: A total of 1563 patients with DTC who underwent first RAI therapy after total or near total thyroidectomy were retrospectively enrolled from 25 hospitals. Response to therapy was evaluated with two different protocols based on combination of biochemical and imaging studies: (1) serum thyroglobulin (Tg) and neck ultrasonography (US) and (2) serum Tg, neck US, and radioiodine scan. The responses to therapy were classified into excellent and non-excellent or acceptable and non-acceptable to minimize the effect of non-specific imaging findings. We investigated which factors were associated with response to therapy depending on the follow-up protocols as well as response classifications. Multivariate logistic regression analysis was performed to identify factors significantly predicting response to therapy. RESULTS: The proportion of patients in the excellent response group significantly decreased from 76.5 to 59.6% when radioiodine scan was added to the follow-up protocol (P < 0.001). Preparation method (recombinant human TSH vs. thyroid hormone withdrawal) was a significant factor for excellent response prediction evaluated with radioiodine scan (OR 2.129; 95% CI 1.687-2.685; P < 0.001) but was not for other types of response classifications. Administered RAI activity, which was classified as low (1.11 GBq) or high (3.7 GBq or higher), significantly predicted both excellent and acceptable responses regardless of the follow-up protocol. CONCLUSIONS: The clinical impact of factors related to response prediction differed depending on the follow-up protocol or classification of response criteria. A high administered activity of RAI was a significant factor predicting a favorable response to therapy regardless of the follow-up protocol or classification of response criteria.

The effect of chronic cerebral hypoperfusion on the pathology of Alzheimer's disease: A positron emission tomography study in rats.

Cerebrovascular disease is a potential risk factor for Alzheimer's disease (AD). Although acute cerebral hypoperfusion causes neuronal necrosis and infarction, chronic cerebral hypoperfusion induces apoptosis in neurons, but its effects on the cognitive impairment are not clear. The purpose of this study was to evaluate the effects of chronic cerebral hypoperfusion on AD pathology and cerebral glucose metabolism. A model of chronic cerebral hypoperfusion was established by ligating the common carotid arteries bilaterally in adult male rats (CAL group). Sham-operated rats underwent the same procedures without artery ligation (control group). At 12 weeks after ligation, expression levels of amyloid-ß (Aß) and hyperphosphorylated tau (p-tau), as well as the regional cerebral glucose metabolism, were evaluated using Western blots and positron emission tomography with fluorine-18 fluorodeoxyglucose, respectively. The expression levels of Aß in the frontal cortex and hippocampus and of p-tau in the temporal cortex were significantly higher in the CAL group than those in the control group. The cerebral glucose metabolism of the amygdala, entorhinal cortex, and hippocampus was significantly decreased in the CAL group compared to that in the control. These results suggest that chronic cerebral hypoperfusion can induce AD pathology and may play a significant role in AD development.

Asociación entre daños en la sustancia blanca y metabolismo de la glucosa cerebral en pacientes con disfunción cognitiva / Association between white matter lesions and the cerebral glucose metabolism in patients with cognitive impairment

OBJETIVO: Los daños en la sustancia blanca (DSB), detectados como hiperintensidades en las imágenes de RM ponderadas en T2, representan la enfermedad de pequeños vasos cerebrales, y están considerados como un factor de riesgo potencial de trastornos de la memoria y disfunción cognitiva. No se ha evidenciado suficientemente que la disfunción cognitiva en pacientes con enfermedad de Alzheimer esté causada por DSB y la patología β-amiloide (Aβ). El objetivo de estudio fue evaluar la relación entre los DSB y el metabolismo de la glucosa cerebral en pacientes con disfunción cognitiva, tras el ajuste de la carga cerebral de Aβ. MATERIALES Y MÉTODOS: Incluimos en este estudio transversal a ochenta y tres sujetos con desempeño cognitivo que oscilaba entre normal y demencia, a quienes se realizó RM cerebral y PET con Florbetaben (18F) y PET con 18F-FDG. Utilizamos la escala Fazekas para cuantificar los DSB en la RM cerebral ponderada en T2. Estimamos cuantitativamente la carga cerebral de Aβ y el metabolismo de la glucosa cerebral utilizando el análisis del volumen de interés. Evaluamos las diferencias del metabolismo de la glucosa cerebral regional entre los grupos de bajo DSB (escala Fazekas<2) y alto DSB (escala Fazekas≥2). Realizamos un análisis de regresión lineal múltiple ajustado por edad, sexo y carga cerebral de Aβ, para evaluar la relación entre la puntuación de la escala Fazekas y el metabolismo de la glucosa cerebral. RESULTADOS: El metabolismo de la glucosa cerebral regional para los lóbulos bilateral frontal, temporal, córtices parietales, y lóbulos límbicos en el grupo de alto DSB fueron significativamente menores que los del grupo de bajo DSB. Existieron correlaciones negativas significativas entre la puntuación de la escala Fazekas y el metabolismo de la glucosa cerebral regional en los córtices bilateral frontal, bilateral temporal y córtices parietales izquierdos, y lóbulos límbicos bilaterales. Los análisis de regresión lineal múltiple revelaron que la puntuación de la escala Fazekas era un determinante independiente del metabolismo de la glucosa en los córtices bilateral frontal y temporal y los lóbulos límbicos. CONCLUSIONES: Los DSB están asociados a un descenso del metabolismo de la glucosa cerebral. Nuestros hallazgos sugieren que la enfermedad de los pequeños vasos, así como lo patología de Aβ, pueden contribuir a la disfunción cognitiva en pacientes con enfermedad de Alzheimer

AIM: White matter lesions (WMLs), detected as hyperintensities on T2-weighted MRI, represent small vessel disease in the brain and are considered a potential risk factor for memory and cognitive impairment. It has not been sufficiently evident that cognitive impairment in patients with Alzheimer's disease is caused by WMLs as well as β-amyloid (Aβ) pathology. The aim of this study was to evaluate relationship between WMLs and cerebral glucose metabolism in patients with cognitive impairment after adjustment of cerebral Aβ burden. MATERIALS AND METHODS: Eighty-three subjects with cognitive performance ranging from normal to dementia, who underwent brain MRI and 18F-florbetaben positron emission tomography (PET) and 18F-fluorodeoxyglucose PET, were included in this cross-sectional study. The Fazekas scale was used to quantify WMLs on brain T2-weighted MRI. The cerebral Aβ burden and cerebral glucose metabolism were quantitatively estimated using volume-of-interest analysis. Differences in the regional cerebral glucose metabolism were evaluated between low-WML (Fazekas scale<2) and high-WML (Fazekas scale≥2) groups. Multiple linear regression analysis adjusted for age, sex and cerebral Aβ burden was performed to evaluate the relationship between the Fazekas scale score and cerebral glucose metabolism. RESULTS: The regional cerebral glucose metabolism for the bilateral frontal, temporal, and parietal cortices, and limbic lobes in the high-WML group were significantly lower than those in the low-WML group. There were significant negative correlations between the Fazekas scale score and regional cerebral glucose metabolism in the bilateral frontal, bilateral temporal and left parietal cortices, and bilateral limbic lobes. Multiple linear regression analysis revealed that the Fazekas scale score was an independent determinant of the glucose metabolism in the bilateral frontal and temporal cortices and limbic lobes. CONCLUSIONS: WMLs are associated with decreased cerebral glucose metabolism. Our findings suggest that small vessel disease, as well as Aβ pathology, may contribute to cognitive impairment in patients with Alzheimer's disease

Comparison of Tc-99m DMSA Renal Planar Scan and SPECT for Detection of Cortical Defects in Infants with Suspected Acute Pyelonephritis.

OBJECTIVE: To compare the detection rate of Tc-99m dimercaptosuccinic acid (DMSA) renal single photon emission computerized tomography (SPECT) with that of planar scan for renal cortical defects in infants under one year of age with suspected acute pyelonephritis. METHODS: Sixty infants under one year of age who exhibited fever and pyuria were prospectively included in this study. All infants underwent concurrent Tc-99m DMSA renal planar scan and SPECT. Detection rates for cortical defects and the numbers of cortical defects in both kidneys were compared between Tc-99m DMSA planar scan and SPECT. The cortical defects were classified as large and small; the rate of discordant results was compared between subgroups. RESULTS: Negative findings by planar scan in 11 infants (11.3%) were modified to positive findings by SPECT. The detection rate of SPECT was significantly higher than that of planar scan (53.3% vs. 35.0%, p < 0.001). The numbers of cortical defects on SPECT were significantly higher than those on planar scan (0.85 ± 0.97 vs. 0.53 ± 0.83, p < 0.001). A significantly higher rate of discordant results between the planar scan and SPECT was observed for the small cortical defects compared to the large cortical defects (48.6% vs. 14.3%, p = 0.029). CONCLUSIONS: Tc-99m DMSA renal SPECT showed a higher detection rate, compared with planar scan, for renal cortical defects in infants with suspected acute pyelonephritis. The study results suggest that, compared with planar scan, Tc-99m DMSA SPECT can detect small cortical defects with greater sensitivity.

Association between white matter lesions and the cerebral glucose metabolism in patients with cognitive impairment. / Asociación entre daños en la sustancia blanca y metabolismo de la glucosa cerebral en pacientes con disfunción cognitiva.

AIM: White matter lesions (WMLs), detected as hyperintensities on T2-weighted MRI, represent small vessel disease in the brain and are considered a potential risk factor for memory and cognitive impairment. It has not been sufficiently evident that cognitive impairment in patients with Alzheimer's disease is caused by WMLs as well as ß-amyloid (Aß) pathology. The aim of this study was to evaluate relationship between WMLs and cerebral glucose metabolism in patients with cognitive impairment after adjustment of cerebral Aß burden. MATERIALS AND METHODS: Eighty-three subjects with cognitive performance ranging from normal to dementia, who underwent brain MRI and 18F-florbetaben positron emission tomography (PET) and 18F-fluorodeoxyglucose PET, were included in this cross-sectional study. The Fazekas scale was used to quantify WMLs on brain T2-weighted MRI. The cerebral Aß burden and cerebral glucose metabolism were quantitatively estimated using volume-of-interest analysis. Differences in the regional cerebral glucose metabolism were evaluated between low-WML (Fazekas scale<2) and high-WML (Fazekas scale≥2) groups. Multiple linear regression analysis adjusted for age, sex and cerebral Aß burden was performed to evaluate the relationship between the Fazekas scale score and cerebral glucose metabolism. RESULTS: The regional cerebral glucose metabolism for the bilateral frontal, temporal, and parietal cortices, and limbic lobes in the high-WML group were significantly lower than those in the low-WML group. There were significant negative correlations between the Fazekas scale score and regional cerebral glucose metabolism in the bilateral frontal, bilateral temporal and left parietal cortices, and bilateral limbic lobes. Multiple linear regression analysis revealed that the Fazekas scale score was an independent determinant of the glucose metabolism in the bilateral frontal and temporal cortices and limbic lobes. CONCLUSIONS: WMLs are associated with decreased cerebral glucose metabolism. Our findings suggest that small vessel disease, as well as Aß pathology, may contribute to cognitive impairment in patients with Alzheimer's disease.

Genetic features associated with 18F-FDG uptake in intrahepatic cholangiocarcinoma.

PURPOSE: In intrahepatic cholangiocarcinoma (iCCA), genetic characteristics on 18F-fluorodeoxyglucose (18F-FDG)-PET scans are not yet clarified. If specific genetic characteristics were found to be related to FDG uptake in iCCA, we can predict molecular features based on the FDG uptake patterns and to distinguish different types of treatments. In this purpose, we analyzed RNA sequencing in iCCA patients to evaluate gene expression signatures associated with FDG uptake patterns. METHODS: We performed RNA sequencing of 22 cases iCCA who underwent preoperative 18F-FDG-PET, and analyzed the clinical and molecular features according to the maximum standard uptake value (SUVmax). Genes and biological pathway which are associated with SUVmax were analyzed. RESULTS: Patients with SUVmax higher than 9.0 (n = 9) had poorer disease-free survival than those with lower SUVmax (n = 13, P = 0.035). Genes related to glycolysis and gluconeogenesis, phosphorylation and cell cycle were significantly correlated with SUVmax (r ≥ 0.5). RRM2, which is related to the toxicity of Gemcitabine was positively correlated with SUVmax, and SLC27A2 which is associated with Cisplastin response was negatively correlated with SUVmax. According to the pathway analysis, cell cycle, cell division, hypoxia, inflammatory, and metabolism-related pathways were enriched in high SUVmax patients. CONCLUSION: The genomic features of gene expression and pathways can be predicted by FDG uptake features in iCCA. Patients with high FDG uptake have enriched cell cycle, metabolism and hypoxic pathways, which may lead to a more rational targeted treatment approach.

Predictive Value of [18F]FDG PET/CT for Lymph Node Metastasis in Rectal Cancer.

[18F]Fluorodeoxyglucose ([18F]FDG) Positron emission tomography/computed tomography (PET/CT) is commonly used for rectal cancer staging, but improved diagnostic methods for nodal metastases are needed. We aimed to evaluate whether the combination model of the metabolic tumor volume of primary tumor (T_MTV) and maximum standardized uptake value of lymph node (N_SUVmax) on pretreatment [18F]FDG PET/CT could improve nodal metastases prediction in rectal cancer. We enrolled a total of 166 rectal cancer patients who underwent pretreatment [18F]FDG PET/CT and surgical resection without neoadjuvant treatment between January 2009 and August 2016. Visual and semiquantitative PET/CT parameters were obtained. Associations between clinicopathological, PET/CT-derived variables and nodal metastases were evaluated by logistic regression analysis. Nodal metastases were confirmed histologically in 68 of the 166 patients (41%). Uni- and multivariate analyses demonstrated T_MTV and N_SUVmax were independent predictive factors for nodal metastases. The c-statistics of the combination model was 0.806 (Standard Error, 0.034; 95% Confidence Interval, 0.737-0.863), which showed significant improvement compared to T_MTV (0.698, P = 0.0002) or N_SUVmax (0.720, P = 0.0008) alone. T_MTV and N_SUVmax are independently correlated with nodal metastases. Furthermore, the combination model showed improved performance for risk prediction; thus, [18F]FDG PET/CT might have a role in rectal cancer staging and treatment planning.

Dietary intake of pantothenic acid is associated with cerebral amyloid burden in patients with cognitive impairment.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by the deposition of amyloid-ß peptide (Aß) in diffuse and neuritic plaques. Previous research has suggested that certain vitamins may prevent this process. In the present study, we evaluated the relationship between vitamin intake and cerebral Aß burden in patients with cognitive impairment. This study included 19 patients with subjective cognitive impairment and 30 patients with mild cognitive impairment. All patients underwent brain MRI and 18F-florbetaben positron emission tomography. The Food Frequency Questionnaire was used to evaluate dietary intake of the 15 vitamins. Intake of vitamin B6 (p = 0.027), vitamin K (p = 0.042), vitamin A (p = 0.063), riboflavin (p = 0.063), ß-carotene (p = 0.081), pantothenic acid (p = 0.092), and niacin (p = 0.097) was higher in the Aß-positive group than in the Aß-negative group. Multivariate linear regression analysis revealed that pantothenic acid intake was an independent determinant of cerebral Aß burden (ß = 0.287, p = 0.029). No significant correlations were observed between cerebral Aß burden and the intake of other vitamins. Our findings demonstrated that pantothenic acid intake may be associated with increased cerebral Aß burden in patients with cognitive impairment. These results may offer insight into potential strategies for AD prevention.