Is cerebral glucose metabolism related to blood-brain barrier dysfunction and intrathecal IgG synthesis in Alzheimer disease?: A 18F-FDG PET/CT study.

The aim of this study was to investigate the relationships between blood-brain barrier (BBB) dysfunction, intrathecal IgG synthesis, and brain glucose consumption as detectable by means of serum/cerebrospinal fluid (CSF) albumin index (Qalb) and IgG index [(CSF IgG/serum IgG) × Serum albumin/CSF albumin)] and 2-deoxy-2-(F) fluoro-D-glucose (F-FDG) positron emission tomography/computed tomography (PET/CT) in a selected population affected by Alzheimer disease (AD). The study included 134 newly diagnosed AD patients according to the NINCDS-ADRDA criteria. The mean (±SD) age of the patients was 70 (±6) years; 60 were male and 64 were female. Mini mental State Examination was equal to 18.9 (±7.2). All patients underwent a CSF assay and magnetic resonance before F-FDG PET scanning. The relationships were evaluated by means of statistical parametric mapping (SPM8). We found a significant negative correlation between the increase of Qalb and F-FDG uptake in the Brodmann Area 42 and 22 that corresponds to the left superior temporal gyrus, with higher Qalb values being related to a reduced glucose consumption in these areas. No significant relationships have been found between brain glucose consumption and IgG index. The results of our study suggest that BBB dysfunction is related to reduction of cortical activity in the left temporal cortex in AD subjects.

Functional correlates of t-Tau, p-Tau and Aß1₋42 amyloid cerebrospinal fluid levels in Alzheimer's disease: a ¹8F-FDG PET/CT study.

AIM: The aim of the study was to investigate the relationships between cerebrospinal fluid (CSF) levels of t-Tau, p-Tau and amyloid-ß (Aß1₋42) amyloid peptide and fluorine-18 fluorodeoxyglucose (¹8F-FDG) brain distribution in a group of patients with Alzheimer's disease. MATERIALS AND METHODS: The study included 81 newly diagnosed Alzheimer's disease patients according to the NINCDS-ADRDA criteria. The mean (±SD) age of the patients was 70 (±6) years; 44 were male and 37 were female. All patients underwent a CSF assay and MRI before ¹8F-FDG PET scanning. The relationships were evaluated by means of statistical parametric mapping (SPM8). RESULTS: Increased t-Tau CSF levels were related to reduced glucose consumption in a wide portion of the right frontal lobe [Brodmann area (BA 47)] and limbic lobe bilaterally (BA 31,32), whereas no areas of increased ¹8F-FDG uptake related to t-Tau levels were detected. Elevated p-Tau concentrations in CSF were related to increased glucose consumption in both the right and the left limbic lobe and in the left frontal lobe (BA 32 and 8). We did not find any specific cortical area of reduced glucose consumption being related to low levels of Aß1₋42 in CSF, whereas a spawn of ¹8F-FDG uptake was detectable in BA 18,19 and in the right cerebellum. CONCLUSION: The results of our study suggest that reduced Aß1₋42 concentrations in CSF are related to a wide cortical dysfunction, whereas t-Tau and p-Tau are related to more selective cortical metabolic patterns that mainly involve the cingulate cortex.

Cortical activity during olfactory stimulation in multiple chemical sensitivity: a (18)F-FDG PET/CT study.

PURPOSE: To investigate the differences in brain glucose consumption during olfactory stimulation between subjects affected by multiple chemical sensitivity (MCS) and a group of healthy individuals. METHODS: Two (18)F-FDG PET/CT scans were performed in 26 subjects (6 men and 20 women; mean age 46.7 ± 11 years) with a clinical diagnosis of MCS and in 11 healthy controls (6 women and 5 men; mean age 45.7 ± 11 years), the first scan after a neutral olfactory stimulation (NS) and the second after a pure olfactory stimulation (OS). Differences in (18)F-FDG uptake were analysed by statistical parametric mapping (SPM2). RESULTS: In controls OS led to an increase in glucose consumption in BA 18 and 19 and a reduction in glucose metabolism in BA 10, 11, 32 and 47. In MCS subjects, OS led to an increase in glucose consumption in BA 20, 23, 18 and 37 and a reduction in glucose metabolism in BA 8, 9 and 10. CONCLUSION: The results of our study suggest that cortical activity in subjects with MCS differs from that in healthy individuals during olfactory stimulation.

Brain metabolic changes in Hodgkin disease patients following diagnosis and during the disease course: An 18F-FDG PET/CT study.

The aim of the present study was to investigate brain glucose metabolism in patients with Hodgkin disease (HD) after diagnosis and during chemotherapy treatment. Following the administration of first-line doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy, 74 HD patients underwent 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/computed tomography brain scans, both baseline (PET0) and interim (PET2) at the Department of Biomedicine and Prevention, University of Rome Tor Vergata (Rome, Italy). Fifty-seven patients were further evaluated 15±6 days after four additional cycles (PET6). Furthermore, a control group (CG) of 40 chemotherapy-naïve subjects was enrolled. Differences in brain 18F-FDG uptake between the CG, PET0, PET2 and PET6 scans were analyzed using statistical parametric mapping. Compared with the PET0 and CG scans, the PET2 scan demonstrated a higher metabolic activity in Brodmann area (BA) 39, and a metabolic reduction in BA 11 bilaterally and in left BA 32. All of these changes disappeared at PET6. The results of the present study indicate that ABVD chemotherapy has a limited impact on brain metabolism.

Factors affecting ¹8F FDOPA standardized uptake value in patients with primary brain tumors after treatment.

AIM: To investigate the factors affecting (18)F FDOPA uptake in patients with primary brain tumors (PBT) after treatment. MATERIALS AND METHODS: 97 patients with PBT (6 were grade I, 40 were grade II, 29 were grade III and 22 were grade IV) underwent (18)F FDOPA positron emission tomography/computed tomography (PET/CT) after treatment. Intervals from surgery, chemotherapy (CHT) and radiotherapy (RT) were 41.48 (±42.27), 16.04 (±29.08) and 28.62 (±34.49) months respectively. RESULTS: (18)F FDOPA uptake in the site of recurrence was not related to the interval from surgery and CHT while a significant relationship has been found with the interval from RT and tumor grade. CONCLUSIONS: The results of our study show that the interval from RT and the grade of PBT should be considered carefully when evaluating brain PET/CT scans since these factors could directly affect (18)F FDOPA uptake.

18-Fluoro-2-deoxyglucose positron emission tomography-computed tomography: an additional tool in the diagnosis of prosthetic valve endocarditis.

OBJECTIVES: To evaluate the role of 18-fluoro-2-deoxyglucose positron emission tomography-computed tomography ((18)F-FDG-PET-CT) in the diagnosis of infectious endocarditis (IE). METHODS: We retrospectively examined 27 consecutive patients who were admitted to the Infectious Diseases Department of Tor Vergata University Hospital between 2009 and 2013 with a suspicion of IE. The final IE diagnosis was defined according to the modified Duke criteria, and the microbiological and diagnostic results were collected for each patient. RESULTS: Twenty out of 27 patients had a suspected prosthetic valve endocarditis (PVE) and seven had a suspected native valve endocarditis (NVE). Twenty-five out of 27 patients (92%) had a confirmed diagnosis of IE (18/25 PVE and 7/25 NVE); 16 had a positive echocardiography evaluation and 16 had positive (18)F-FDG-PET-CT findings. Echocardiography showed a higher sensitivity as a diagnostic tool for the detection of IE compared to (18)F-FDG-PET-CT (80% vs. 55%). However, a greater number of PVE had positive (18)F-FDG-PET-CT results compared to those with positive echocardiography findings (11/13 vs. 9/13), and overall 89% (16/18) of confirmed PVE resulted (18)F-FDG-PET-CT positive. Analyzing only the cases who underwent transoesophageal echocardiography, (18)F-FDG-PET-CT showed a sensitivity of 85% in PVE (vs. 69% for echocardiography and 77% for the Duke criteria). All seven patients with NVE had a positive echocardiography and negative (18)F-FDG-PET-CT findings (p<0.001). CONCLUSIONS: The results of this study further highlight the limitations of echocardiography in the diagnosis of PVE and the potential advantages of (18)F-FDG-PET-CT in these cases.

Cerebellar metabolic involvement and its correlations with clinical parameters in vestibular neuritis.

Although vestibular neuritis (VN) cortical models are described in the literature, there is lack of knowledge regarding the exclusive cerebellar involvement. The aim of the present study was to analyze, by [18F] fluorodeoxyglucose-positron emission tomography (FDG-PET)/computer tomography, regional cerebellar FDG uptake in eight right-handed VN patients (five females; three males; mean age 48 ± 7 years) during the first few days (PET0) and after 1 month (PET1) since symptoms onset. At both phases, patients underwent otoneurological examination and filled in a battery of validated questionnaires. Twenty-six cerebellar volumes of interest (VOI) were identified by the automated anatomical labeling library and normalized to thalamus FDG-PET uptake. Mean intensity within VOIs was calculated in both phases and processed by within-subjects ANOVA. A significantly lower (p < 0.005) FDG uptake distribution was found in bilateral lobules III, VI and X and in vermis 1-2, 3, 6 and 10 at PET0 as compared to PET1 and a significant higher FDG uptake distribution was found in right crus I in the same comparison. Significant (p < 0.05) positive correlations were found between Anxiety and Bucket test scores, and normalized metabolism in right crus I (at PET0) and vermis 10 (at PET1), respectively. A negative correlation was found at PET0 between slow-phase velocity scores and normalized metabolism in right lobule X. These data show relevant changes in the pattern of cerebellar metabolism that might unravel additional central aspects of early and late VN associated to bilateral cortical responses to sensory conflict during the acute VN-related controversial inflow.

Cortico-subcortical metabolic correlates of olfactory processing in healthy resting subjects.

A wide network of interconnected areas was previously found in neuroimaging studies involving normal as well as pathological subjects; however literature seems to suffer from a lack of investigation in glucose metabolism behaviour under olfactory condition. Thus, the present work describe for the first time a pure olfactory related brain response of metabolism by using (18)F-fluorodeoxyglucose-Positron Emission Tomography/Computer Tomography in eleven resting subjects undergoing a neutral and a pure olfactory condition. By contrasting these experimental phases, it was possible to depict a re-organization pattern of default mode network structures in a relatively ecological environment. Moreover, by correlating such pattern with a battery of validated olfactory and neuropsychological tests, our work allowed in showing peculiar correlation data that could cluster the subjects sample in a certain range of normality. We believe the present study could integrate the current knowledge in olfactory research and could be a start-up for future contributions.

Factors affecting intrapatient liver and mediastinal blood pool ¹8F-FDG standardized uptake value changes during ABVD chemotherapy in Hodgkin's lymphoma.

PURPOSE: The aim of our study was to assess the intrapatient variability of 2-deoxy-2-((18)F)-fluoro-D-glucose ((18)F-FDG) uptake in the liver and in the mediastinum among patients with Hodgkin's lymphoma (HL) treated with doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy (CHT). METHODS: The study included 68 patients (30 men, 38 women; mean age 32 ± 11 years) with biopsy-proven HL. According to Ann Arbor criteria, 6 were stage I, 34 were stage II, 12 were stage 3 and 16 were stage 4. All of them underwent a baseline (PET0) and an interim (PET2) (18)F-FDG whole-body positron emission tomography (PET)/CT. All patients were treated after PET0 with two ABVD cycles for 2 months that ended 15 ± 5 days prior to the PET2 examination. All patients were further evaluated 15 ± 6 days after four additional ABVD cycles (PET6). None of the patients presented a serum glucose level higher than 107 mg/dl. The mean and maximum standardized uptake values (SUV) of the liver and mediastinum were calculated using the same standard protocol for PET0, PET2 and PET6, respectively. Data were examined by means of the Wilcoxon matched pairs test and linear regression analysis. RESULTS: The main results of our study were an increased liver SUVmean in PET2 (1.76 ± 0.35) as compared with that of PET0 (1.57 ± 0.31; p < 0.0001) and PET6 (1.69 ± 0.28; p = 0.0407). The same results were obtained when considering liver SUVmax in PET2 (3.13 ± 0.67) as compared with that of PET0 (2.82 ± 0.64; p < 0.0001) and PET6 (2.96 ± 0.52; p = 0.0105). No significant differences were obtained when comparing mediastinum SUVmean and SUVmax in PET0, PET2 and PET6 (p > 0.05). Another finding is a relationship in PET0 between liver SUVmean and SUVmax with the stage, which was lower in those patients with advanced disease (r (2) = 0.1456 and p = 0.0013 for SUVmean and r (2) = 0.1277 and p = 0.0028 for SUVmax). CONCLUSION: The results of our study suggest that liver (18)F-FDG uptake is variable in patients with HL during the CHT treatment and the disease course and should be considered carefully when used to define the response to therapy in the interim PET in HL.

A new natural history of Charcot foot: clinical evolution and final outcome of stage 0 Charcot neuroarthropathy in a tertiary referral diabetic foot clinic.

PURPOSE: The purpose of this study is to describe the usefulness of 18F-FDG PET/CT scanning in the diagnosis and follow-up of stage 0 Charcot foot (CNO) and CNO outcomes when therapeutic options are driven by this image modality. PATIENTS AND METHODS: We selected 25 out of 40 diabetic patients with an acute CNO, without any bone involvement at x-ray (stage 0 CNO). Diagnostic criteria were inflammatory clinical signs of the affected foot and skin temperature difference greater than 2°C compared with the contralateral foot (ΔT). All patients underwent x-ray, MRI, and 18F-FDG PET/CT scanning (expressed as standardized uptake value, SUVmax) at baseline (T0). All patients underwent another 18F-FDG PET/CT within 1 month after ΔT was less than 2°C [clinical recovery (T1)] and again every 3 months until SUVmax was less than 2 [final recovery (T2)]; at this time, MRI confirmed the end of the inflammatory condition. RESULTS: T0 ΔT was 3.04 ± 1.65°C. All patients showed T0 SUVmax of the affected foot higher than the contralateral one (3.83 ± 1.087 vs. 1.24 ± 0.3; P < 0.001). At clinical recovery (T1), defined by ΔT below 2°C, the inflammatory signs were no longer present (T0 vs. T1 ΔT = 3.04 ± 1.65 vs. 0.9 ± 0.55°C; P < 0.0001). At T1, SUVmax was unchanged from T0 (3.80 ± 1.69 vs. 3.83 ± 1.09; P = ns). At final recovery (T2), ΔT was 0.74 ± 0.29°C (similar to T1 ΔT), while the SUVmax dropped from T1 to T2 (3.8 ± 1.69 vs. 1.72 ± 0.52; P < 0.0001). Standard therapy was total contact cast and removable cast walker until T2 (15.12 ± 5.45 mo). No patient developed foot bone fractures nor had relapses during follow-up (21.75 ± 16.7 mo). DISCUSSION: PET/CT scan allows the quantification of the inflammatory process; therefore, it may drive clinical decisions in the management of acute CNO better than clinical criteria. None of our patients developed foot bone fractures or had relapses during follow-up driven by PET/CT scan.

Early and phasic cortical metabolic changes in vestibular neuritis onset.

Functional brain activation studies described the presence of separate cortical areas responsible for central processing of peripheral vestibular information and reported their activation and interactions with other sensory modalities and the changes of this network associated to strategic peripheral or central vestibular lesions. It is already known that cortical changes induced by acute unilateral vestibular failure (UVF) are various and undergo variations over time, revealing different cortical involved areas at the onset and recovery from symptoms. The present study aimed at reporting the earliest change in cortical metabolic activity during a paradigmatic form of UVF such as vestibular neuritis (VN), that is, a purely peripheral lesion of the vestibular system, that offers the opportunity to study the cortical response to altered vestibular processing. This research reports [(18)F]fluorodeoxyglucose positron emission tomography brain scan data concerning the early cortical metabolic activity associated to symptoms onset in a group of eight patients suffering from VN. VN patients' cortical metabolic activity during the first two days from symptoms onset was compared to that recorded one month later and to a control healthy group. Beside the known cortical response in the sensorimotor network associated to vestibular deafferentation, we show for the first time the involvement of Entorhinal (BAs 28, 34) and Temporal (BA 38) cortices in early phases of symptomatology onset. We interpret these findings as the cortical counterparts of the attempt to reorient oneself in space counteracting the vertigo symptom (Bas 28, 34) and of the emotional response to the new pathologic condition (BA 38) respectively. These interpretations were further supported by changes in patients' subjective ratings in balance, anxiety, and depersonalization/derealization scores when tested at illness onset and one month later. The present findings contribute in expanding knowledge about early, fast-changing, and complex cortical responses to pathological vestibular unbalanced processing.

Cardiac sympathetic denervation is not related to nigrostriatal degeneration in Parkinson's disease.

AIM: The aim of our study was to investigate the relationship between myocardial sympathetic degeneration and nigrostriatal impairment in patients affected by Parkinson's disease (PD) by means of (123)I-metaiodobenzylguanidine ((123)I MIBG) scintigraphy and N-(3-fluoropropyl)-2ß-carbomethoxy-3ß-(4-[(123)I]iodophenyl)nortropane ((123)I FP-CIT) scintigraphy. PATIENTS AND METHODS: The study involved 37 patients with clinical diagnosis of PD (22 males and 15 females, mean age 62 years (±10), evaluated with (123)I FP-CIT single photon emission computed tomography (SPECT) followed by (123)I MIBG scintigraphy within 20 (±3) days. Early and delayed anterior chest images were acquired and the heart/mediastinum ratio (H/M ratio) was calculated. Furthermore, the population has been divided on the basis of the main clinical pattern to investigate the possible role of a tremor-dominant or an akinetic-dominant phenotype in this comparison. RESULTS: In PD population, there were no statistical relationships between early and delayed (123)I MIBG cardiac and (123)I FP-CIT striatal uptake in contralateral caudate (P > 0.05) and in contralateral putamen (P > 0.05) to the side mainly affected; no statistically significant relationships have been found at any level when considering ipsilateral striatum. We did not find statistically significant relationships when considering the single PD phenotypes. CONCLUSIONS: The results of our study suggest that cardiac sympathetic system and nigrostriatal system are differently affected in PD. In particular, the sympathetic neurodegeneration rate is not related to nigrostriatal degeneration rate and vice versa in our series as detectable scintigraphically.

Is cerebral glucose metabolism affected by chemotherapy in patients with Hodgkin's lymphoma?

OBJECTIVE: The aim of the study was to investigate the effect of chemotherapy treatment with ABVD on brain glucose metabolism in patients with Hodgkin's disease (HD). METHODS: A total of 49 patients (23 men, 26 women; mean age 32±9 years) diagnosed with HD were included in the study. All of them underwent a baseline (PET0) and an interim (PET2) 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) PET/computed tomography (CT) brain scan. All patients were treated after PET0 with two cycles of ABVD consisting of doxorubicin (adriamycin), bleomycin, vinblastine, and dacarbazine for 2 months. Thirty-five patients were evaluated further 15±6 days after four additional cycles (PET6). Differences in brain (18)F-FDG uptake were analyzed by statistical parametric mapping (SPM2). RESULTS: Compared with PET0, PET2 showed a significantly higher metabolic activity in the right angular gyrus (Brodmann area 39) and a significant metabolic reduction in Brodmann areas 10, 11, and 32 bilaterally. All these changes disappeared at PET6. CONCLUSION: Our results support the conclusion of a very limited impact of ABVD chemotherapy on brain metabolism in patients with HD.

Molecular imaging of brain tumors with 18F-DOPA PET and PET/CT.

The objective of this study was to give an overview of the potential clinical utility of [18F]-L-dihydroxyphenylalanine (18F-DOPA) PET and PET/CT for imaging of brain tumors. Review articles and reference lists were used to supplement the search findings. 18F-DOPA has been investigated as a PET tracer for primary brain tumors, metastases of somatic cancer, and evaluation of relapse of pathology in patients with brain tumor after surgery and/or radiotherapy on the basis of enhanced cell proliferation. Available studies have provided encouraging preliminary results for diagnosis of brain tumors and relapse after surgery/radiotherapy. In the brain, excellent discrimination between tumor and normal tissue can be achieved because of the low physiological uptake of 18F-DOPA and the high ratio between tumor and normal hemispheric tissue. Information on evaluation of brain metastases is limited but encouraging. PET and PET/CT with 18F-DOPA are useful in diagnosing primary brain tumors and should be recommended in the diagnosis of relapse of disease after surgical treatment and/or radiotherapy. Semiquantitative analysis could improve diagnosis while correlative imaging with MRI is essential. Limits are due to low knowledge of potential pitfalls.

High-resolution, hand-held camera for sentinel-node detection.

BACKGROUND: The imaging probe (IP) is a high-resolution (HR), 1-in(2) field-of-view hand-held gamma camera. We used it to detect breast cancer sentinel node (SN). PATIENTS AND METHODS: We divided 120 T1 breast cancer patients, who underwent Anger camera lymphoscintigraphy (ACL), in two subgroups of 60 patients who were age, body mass index, and cancer size matched: subgroup A (SA) and B (SB). SN was detected with a common gamma probe (GP) in SA, with IP plus GP in SB. RESULTS: Surgeons removed radioactive nodes without exceeding four nodes. Eighty-two (82) SNs were taken off in SA and 105 in SB (p<0.01). Of SA, 22 of 60 patients and 36 of 60 patients of SB showed more than 1 node, and 3 of them showed 3 nodes and 1 showed 4 nodes. Thirteen (13) patients resulted N(+) (21.6%) in SA. Ten (10) patients of SA showed an invasion on the hottest nodes and 3 on the second nodes. In the SB, 18 patients (25%) showed invasion. Sixteen (16) invasions were on hot, 4 on second, and 1 on the third node. Withdrawal time of SN was 11.25+/-4.7 minutes for SA and 7.4+/-2.8 minutes for SB (p<0.025). CONCLUSIONS: SN biopsy with IP is fast and discovers more SNs and more invasions than ACL.

[Day surgery in a multidisciplinary breast unit]. / Day surgery nell'unità multidisciplinare di senologia.

The most recent studies on breast surgery have led us to radio-guided surgery which enables us to identify the sentinel lymph node and thus to remove just a single lymph node. As a result, we are moving in the direction of an increasingly conservative surgical technique which may be carried out in the day surgery setting. This kind of surgery requires both an extremely accurate and prompt diagnosis and a multidisciplinary breast unit, inasmuch as only the collaboration and teamwork of highly qualified staff are capable of furnishing a rapid, accurate diagnosis; in addition, during the operation it may be necessary to perform x-rays or ultrasonography on the surgical specimen. Obviously, nuclear medicine is essential for radio-guided surgery. We report here on our experience with 36,000 women with 1,147 carcinomas whose diameters were less than or equal to 2 cm in 78.64% of the cases, with the possibility of performing conservative surgery in such cases. Moreover, by way of confirmation of the good diagnostic accuracy, we report our findings in 954 lesions operated on under local anaesthesia, because they were presumed to be most probably or definitely benign, but which tended to increase in volume. During the final histological examination only 10 of these 954 lesions turned out to be malignant, with only a 1.05% incidence of diagnostic error.