Agostino Chiaravalloti

18F-choline PET/CT pitfalls in image interpretation: An update on 300 examined patients with prostate cancer

Objectives 18F-choline PET/CT is an important diagnostic tool in the management of patients with prostate cancer (PC). The aim of this study was to describe and discuss some abnormal sites of uptake that we observed, not due to PC recurrence. Patients and Methods Three hundred patients were submitted to 18F-choline PET/CT for staging or restaging of PC. Whole-body PET/CT was acquired 40 minutes after the 18F-choline administration. Results We found abnormal uptake of the tracer, not related to PC, in 48/300 patients (16%). Most of these findings were due to inflammatory processes. Furthermore, some malignant conditions, such as a case of colon cancer, a case of bladder carcinoma, and a multiple myeloma, were diagnosed. Mild uptake was also detected in some benign diseases, such as thymoma, adrenal adenoma, and sarcoidosis. Six patients showed focal brain uptake in correspondence to a meningioma. Conclusions It is necessary for nuclear physicians, during clinical practice, to consider the possibility of 18F-choline uptake in some benign or malignant conditions for the intrinsic pharmacologic property of the tracer. An accurate medical investigation, correlative imaging with CT and/or MRI with contrast agents, laboratory data, and above all, histologic examination are often necessary for correct diagnosis.

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 [18F]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.

Different patterns of nigrostriatal degeneration in tremor type versus the akinetic-rigid and mixed types of Parkinson's disease at the early stages: Molecular imaging with 123I-FP-CIT SPECT

The various associations of motor and non-motor symptoms, the onset of motor complications, the cognitive disorders appearance and other factors make Parkinsons disease (PD) a heterogeneous syndrome with multiple phenotypes. The necessity of discriminating between different forms of PD could have a role in understanding the pathophysiology of extrapyramidal signs with clinical implications. The aim of this study was to evaluate if there is a relationship between the clinical motor phenotypes of PD and the scintigraphic pattern of 123I-FP-CIT single photon emission computed tomography (SPECT). We examined 47 patients with early idiopathic PD (25 males; 22 females; mean age 58±2 years) and subdivided them in different clinical forms on the basis of dominance of resting tremor (n=20), bradykinesia plus rigidity (n=20) and the presence of both clinical signs [mixed type (MT, n=7)]. We correlated this status with the semi-quantitative analysis of SPECT with 123I-FP-CIT. Tremor type patients showed a lower reduction of 123I-FP-CIT uptake compared to akinetic-rigid type patients in contralateral caudate (P=0.0139) and putamen (P=0.0028) nuclei. 123I-FP-CIT uptake was higher in the ipsilateral caudate (P=0.0050) and putamen (P=0.0012) of tremor type patients compared to akinetic-rigid type patients. Comparisons of the striatal uptake in the tremor type and akinetic-rigid type patients with the MT patients revealed significant differences only in the ipsilateral and contralateral caudate. Our data indicate that in akinetic-rigid patients the dopaminergic system is more involved compared to that in the tremor type patients and that this difference is present from the initial stage of the disease. Moreover, our results suggest that PD phenotypes could be related not only to the dopaminergic involvement but also to other systems.

Cerebrospinal fluid lactate levels and brain [18F]FDG PET hypometabolism within the default mode network in Alzheimer’s disease

PurposeIt has been suggested that neuronal energy metabolism may be involved in Alzheimer’s disease (AD). In this view, the finding of increased cerebrospinal fluid (CSF) lactate levels in AD patients has been considered the result of energetic metabolism dysfunction. Here, we investigated the relationship between neuronal energy metabolism, as measured via CSF lactate levels, and cerebral glucose metabolism, as stated at the 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography ([18F]FDG PET) in AD patients.MethodsAD patients underwent lumbar puncture to measure CSF lactate levels and [18F]FDG PET to assess brain glucose metabolism. CSF and PET data were compared to controls. Since patients were studied at rest, we specifically investigated brain areas active in rest-condition owing to the Default Mode Network (DMN). We correlated the CSF lactate concentrations with the [18F]FDG PET data in brain areas owing to the DMN, using sex, age, disease duration, Mini Mental State Examination, and CSF levels of tau proteins and beta-amyloid as covariates.ResultsAD patients (n = 32) showed a significant increase of CSF lactate levels compared to Control 1 group (n = 28). They also showed brain glucose hypometabolism in the DMN areas compared to Control 2 group (n = 30). Within the AD group we found the significant correlation between increased CSF lactate levels and glucose hypometabolism in Broadman areas (BA) owing to left medial prefrontal cortex (BA10, mPFC), left orbitofrontal cortex (BA11, OFC), and left parahippocampal gyrus (BA 35, PHG).ConclusionWe found high CSF levels of lactate and glucose hypometabolism within the DMN in AD patients. Moreover, we found a relationship linking the increased CSF lactate and the reduced glucose consumption in the left mPFC, OFC and PHG, owing to the anterior hub of DMN. These findings could suggest that neural glucose hypometabolism may affect the DMN efficiency in AD, also proposing the possible role of damaged brain energetic machine in impairing DMN.

Involvement of Subcortical Brain Structures During Olfactory Stimulation in Multiple Chemical Sensitivity.

Multiple chemical sensitivity (MCS) patients usually react to odour compounds and the majority of neuroimaging studies assessed, especially at the cortical level, many olfactory-related correlates. The purpose of the present study was to depict sub-cortical metabolic changes during a neutral (NC) and pure (OC) olfactory stimulation by using a recently validated 18F-2-fluoro-2-deoxy-d-glucose (FDG)-positron emission tomography/computer tomography procedure in 26 MCS and 11 healthy (HC) resting subjects undergoing a battery of clinical tests. Twelve subcortical volumes of interest were identified by the automated anatomical labeling library and normalized to thalamus FDG uptake. In both groups, when comparing OC to NC, the within-subjects ANOVA demonstrated a relative decreased metabolism in bilateral putamen and hippocampus and a relative increased metabolism in bilateral amygdala, olfactory cortex (OLF), caudate and pallidum. The between-groups ANOVA demonstrated in MCS a significant higher metabolism in bilateral OLF during NC. As in HC subjects negative correlations were found in OC between FDG uptake in bilateral amygdala and hippocampus and odor pleasantness scale, the latter positively correlated with MCS subjects’ bilateral putamen FDG uptake in OC. Besides FDG uptake resemblances in both groups were found, for the first time a relative higher metabolism increase in OLF in MCS subjects at rest with respect to HC was found. When merging this aspect to the different subcortical FDG uptake correlations patterns in the two groups, the present study demonstrated to describe a peculiar metabolic index of behavioral and neurological aspects of MCS complaints.

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.

Different patterns of cardiac sympathetic denervation in tremor-type compared to akinetic-rigid-type Parkinson's disease: Molecular imaging with 123I-MIBG

The aim of this study was to evaluate the correlation between the clinical motor phenotypes of Parkinsons disease (PD) and ¹²³I-MIBG myocardial uptake. In total, 53 patients with PD [31 males and 22 females, mean age 62±10 years; 19 Hoehn & Yahr (H&Y) stage 1, 9 stage 1.5, 15 stage 2 and 10 at stage 3] were examined and subdivided into different clinical forms on the basis of dominance of resting tremor (n=19, TDT) and bradykinesia plus rigidity (n=34, ART). This status was correlated with the semi-quantitative analysis of ¹²³I-MIBG myocardial uptake. An age-matched control group of 18 patients was recruited (8 males and 10 females, mean age 62.4±16.3 years). ¹²³I-MIBG myocardial uptake significantly correlated with disease duration in early (r²=0.1894; P=0.0028) and delayed images (r²=0.1795; P=0.0037) in PD patients, while no correlation was found when considering age at examination, UPDRS III motor examination section score and H&Y score. PD patients showed a reduced ¹²³I-MIBG myocardial uptake compared to the control group in early (P=0.0026) and delayed images (P=0.0040), and ¹²³I-MIBG myocardial uptake was significantly lower in delayed images in TDT patients compared with ART patients (P=0.0167). A decrease was detected in the heart-to-mediastinum (H/M) ratio in delayed images compared to that of the early images in TDT patients (P=0.0040) and in the whole PD population (P=0.0012), while no differences were found in ART patients (P=0.1043). The results of the present study revealed that the cardiac sympathetic system is more severely impaired in TDT than in ART patients and ¹²³I-MIBG molecular imaging has the potential help in improving therapeutic planning in these patients.

Autonomic Function Tests and MIBG in Parkinson's Disease: Correlation to Disease Duration and Motor Symptoms.

Disorders of the autonomic nervous system (ANS) have a variable degree of clinical relevance in patients with Parkinsons disease (PD). Here, we assessed whether subclinical autonomic dysfunction, as evaluated by a complete battery of autonomic function tests (AFTs), correlates with PD progression.

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

ObjectiveThe 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). MethodsA 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-[18F]fluoro-D-glucose (18F-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 18F-FDG uptake were analyzed by statistical parametric mapping (SPM2). ResultsCompared 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. ConclusionOur results support the conclusion of a very limited impact of ABVD chemotherapy on brain metabolism in patients with HD.

Functional correlates of t-Tau, p-Tau and Aβ1-42 amyloid cerebrospinal fluid levels in Alzheimer's disease: A 18F-FDG PET/CT study

AimThe aim of the study was to investigate the relationships between cerebrospinal fluid (CSF) levels of t-Tau, p-Tau and amyloid-&bgr; (A&bgr;1–42) amyloid peptide and fluorine-18 fluorodeoxyglucose (18F-FDG) brain distribution in a group of patients with Alzheimer’s disease. Materials and methodsThe 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). ResultsIncreased 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 A&bgr;1–42 in CSF, whereas a spawn of 18F-FDG uptake was detectable in BA 18,19 and in the right cerebellum. ConclusionThe results of our study suggest that reduced A&bgr;1–42 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.