Eleonora Vanzi

Interaction of caudate dopamine depletion and brain metabolic changes with cognitive dysfunction in early Parkinson's disease

Damage to nonmotor dopamine (DA)-mediated frontostriatal circuits has been proposed as the main pathophysiological basis of cognitive dysfunction in Parkinsons disease (PD). In the present study, 18 early nondemented drug naive PD patients were investigated, by dual-tracer N-ω-fluoropropyl-2β-carbomethoxy-3β-4-[123I]iodophenyl-nortropane ([123I]FP-CIT) single-photon emission computed tomography (SPECT)/[18F] fluoro-deoxyglucose (FDG) positron emission tomography (PET) imaging, to test whether an early and not yet treatment-modulated relation exists between cognitive functions, caudate nucleus (CN) DA impairment and brain metabolism (CMRglc) in associative frontostriatal circuits. Verbal fluency performance correlated with DA impairment in CN, and with CMRglc in dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). Further, CMRglc in orbitofrontal cortex, DLPFC, and ACC was shown to be early modulated by the level of DA impairment in CN. The present study demonstrates in vivo the early functional disruption of nonmotor frontostriatal circuits in PD. The effect of CN DA impairment on DLPFC and ACC metabolism is proposed as a possible early pathophysiological and functional substrate for executive dysfunction in PD.

Brain metabolic correlates of dopaminergic degeneration in de novo idiopathic Parkinson’s disease

PurposeThe aim of the present study was to evaluate the reciprocal relationships between motor impairment, dopaminergic dysfunction, and cerebral metabolism (rCMRglc) in de novo Parkinson’s disease (PD) patients.MethodsTwenty-six de novo untreated PD patients were scanned with 123I-FP-CIT SPECT and 18F-FDG PET. The dopaminergic impairment was measured with putaminal 123I-FP-CIT binding potential (BP), estimated with two different techniques: an iterative reconstruction algorithm (BPOSEM) and the least-squares (LS) method (BPLS). Statistical parametric mapping (SPM) multiple regression analyses were performed to determine the specific brain regions in which UPDRS III scores and putaminal BP values correlated with rCMRglc.ResultsThe SPM results showed a negative correlation between UPDRS III and rCMRglc in premotor cortex, and a positive correlation between BPOSEM and rCMRglc in premotor and dorsolateral prefrontal cortex, not surviving at multiple comparison correction. Instead, there was a positive significant correlation between putaminal BPLS and rCMRglc in premotor, dorsolateral prefrontal, anterior prefrontal, and orbitofrontal cortex (p < 0.05, corrected for multiple comparison).ConclusionsPutaminal BPLS is an efficient parameter for exploring the correlations between PD severity and rCMRglc cortical changes. The correlation between dopaminergic degeneration and rCMRglc in several prefrontal regions likely represents the cortical functional correlate of the dysfunction in the motor basal ganglia-cortical circuit in PD. This finding suggests focusing on the metabolic course of these areas to follow PD progression and to analyze treatment effects.

125I-Radiolabeled Morpholine-Containing Arginine–Glycine–Aspartate (RGD) Ligand of αvβ3 Integrin As a Molecular Imaging Probe for Angiogenesis

In this paper, using a hybrid small-animal Micro SPECT/CT imaging system, we report that a new (125)I-Cilengitide-like RGD-cyclopentapeptide, containing d-morpholine-3-carboxylic acid, interacts in vivo with α(v)β(3) integrin expressed by melanoma cells. Images clearly show that the (125)I-compound has the capacity to monitor the growth of a melanoma xenograft. Indeed, retention of the labeled ligand in the tumor mass has a good tumor/background ratio, and a significant reduction of its uptake was observed after injection of unlabeled ligand. These results suggest that the use of (125)I-labeled morpholine-based RGD-cyclopentapeptides targeting α(v)β(3) positive tumors may play a role in future therapeutic strategies.

A direct ROI quantification method for inherent PVE correction: accuracy assessment in striatal SPECT measurements

PurposeThe clinical potential of striatal imaging with dopamine transporter (DAT) SPECT tracers is hampered by the limited capability to recover activity concentration ratios due to partial volume effects (PVE). We evaluated the accuracy of a least squares method that allows retrieval of activity in regions of interest directly from projections (LS-ROI).MethodsAn Alderson striatal phantom was filled with striatal to background ratios of 6:1, 9:1 and 28:1; the striatal and background ROIs were drawn on a coregistered X-ray CT of the phantom. The activity ratios of these ROIs were derived both with the LS-ROI method and with conventional SPECT EM reconstruction (EM-SPECT). Moreover, the two methods were compared in seven patients with motor symptoms who were examined with N-3-fluoropropyl-2-β-carboxymethoxy-3-β-(4-iodophenyl) (FP-CIT) SPECT, calculating the binding potential (BP).ResultsIn the phantom study, the activity ratios obtained with EM-SPECT were 3.5, 5.3 and 17.0, respectively, whereas the LS-ROI method resulted in ratios of 6.2, 9.0 and 27.3, respectively. With the LS-ROI method, the BP in the seven patients was approximately 60% higher than with EM-SPECT; a linear correlation between the LS-ROI and the EM estimates was found (r = 0.98, p = 0.03). ConclusionThe LS-ROI PVE correction capability is mainly due to the fact that the ill-conditioning of the LS-ROI approach is lower than that of the EM-SPECT one. The LS-ROI seems to be feasible and accurate in the examination of the dopaminergic system. This approach can be fruitful in monitoring of disease progression and in clinical trials of dopaminergic drugs.

A proton Computed Tomography system for medical applications

Proton Computed Tomography (pCT) can improve the accuracy of both patient positioning and dose calculation in proton therapy, enabling to accurately reconstruct the electron density distribution of irradiated tissues. A pCT prototype, equipped with a silicon tracker and a YAG:Ce calorimeter, has been manufactured by an Italian collaboration. First tests under proton beam allowed obtaining good quality tomographic images of a non-homogeneous phantom. Manufacturing of a new large area system with real-time data acquisition is under way.

A PPAR-gamma agonist attenuates pulmonary injury induced by irradiation in a murine model.

PURPOSE/OBJECTIVE(S) Due to its anti-inflammatory, antifibrotic and antineoplastic properties, the PPAR-γ agonist rosiglitazone is of interest in the prevention and therapy of radiation-induced pulmonary injury. We evaluated the radioprotective effects of rosiglitazone in a murine model of pulmonary damage to determine whether radioprotection was selective for normal and tumor tissues. METHODS Lungs in C57BL/6J mice were irradiated (19 Gy) with or without rosiglitazone (RGZ, 5mg/kg/day for 16 weeks, oral gavage). Computed tomography (CT) was performed and Hounsfield Units (HU) were determined during the observation period. Histological analysis and evaluation of fibrosis/inflammatory markers by western blot were performed at 16 weeks. A549 tumor-bearing CD1 mice were irradiated (16 Gy) with or without RGZ, and tumor volumes were measured at 35 days. RESULTS Rosiglitazone reduced radiologic and histologic signs of fibrosis, inflammatory infiltrate, alterations to alveolar structures, and HU lung density that was increased due to irradiation. RGZ treatment also significantly decreased Col1, NF-kB and TGF-β expression and increased Bcl-2 protein expression compared to the irradiation group and reduced A549 clonogenic survival and xenograft tumor growth. CONCLUSIONS Rosiglitazone exerted a protective effect on normal tissues in radiation-induced pulmonary injury, while irradiated lung cancer cells were not protected in vivo and in vitro. Thus, rosiglitazone could be proposed as a radioprotective agent in the treatment of lung cancer.

A proton Computed Tomography based medical imaging system

This paper reports on the activity of the INFN PRIMA/RDH collaboration in the development of proton Computed Tomography (pCT) systems based on single proton tracking and residual energy measurement. The systems are made of a silicon microstrip tracker and a YAG:Ce crystal calorimeter to measure single protons trajectory and residual energy, respectively. A first prototype of pCT scanner, with an active area of about 5 × 5 cm2 and a data rate capability of 10 kHz, has been constructed and characterized with 62 MeV protons at INFN Laboratori Nazionali del Sud in Catania (Italy) and with 180 MeV protons at The Svedberg Laboratory (TSL) in Uppsala (Sweden). Results of these measurements, including tomographic reconstructions of test phantoms, will be shown and discussed. An upgraded system with an extended field of view (up to ~ 5 × 20 cm2) and an increased event rate capability up to one MHz, presently under development, will be also described.

Clinical correlation of the binding potential with 123I-FP-CIT in de novo idiopathic Parkinson’s disease patients

PurposeThe aim of this study was to evaluate the accuracy of different single-photon emission computed tomography (SPECT) reconstruction techniques in measuring striatal N-ω-fluoropropyl-2β-carbomethoxy-3β-4-[123I]iodophenyl-nortropane (123I-FP-CIT) binding in de novo Parkinson’s disease (PD) patients, in order to find a correlation with clinical scales of disease severity in the initial phases of disease.MethodsThirty-six de novo PD patients underwent 123I-FP-CIT SPECT and MRI scan. SPECT data were reconstructed with filtered back projection (FBP), with an iterative algorithm (ordered subset expected maximization, OSEM) and with a method previously developed in our institution, called least-squares (LS) method. The ratio of specific to non-specific striatal 123I-FP-CIT binding (binding potential, BP) was used as the outcome measure with all the reconstruction methods (BPFBP, BPOSEM, BPLS).ResultsThe range of values of striatal BPLS was significantly greater than BPFBP and BPOSEM. For all striatal regions, estimates of BPFBP correlated well with BPOSEM (r = 0.84) and with BPLS (r = 0.64); BPOSEM correlated significantly with BPLS (r = 0.76). A good correlation was found between putaminal BPLS and Hoen and Yahr, Unified PD Rating Scale (UPDRS) and lateralized UPDRS motor scores (r = −0.46, r = −0.42, r = −0.39, respectively). Neither putaminal BPFBP nor putaminal BPOSEM correlated with any of these motor scores.ConclusionsIn de novo PD patients, 123I-FP-CIT BP values derived from FBP and OSEM reconstruction techniques do not permit to differentiate PD severity. The LS method instead finds a correlation between striatal BP and disease severity scores. The results of this study support the use of 123I-FP-CIT BP values estimated with the LS method as a biomarker of PD severity.

(18)F-FDG PET/CT quantification in head and neck squamous cell cancer: principles, technical issues and clinical applications.

Abstract18F-FDG PET/CT plays a crucial role in the diagnosis and management of patients with head and neck squamous cell cancer (HNSCC). The major clinical applications of this method include diagnosing an unknown primary tumour, identifying regional lymph node involvement and distant metastases, and providing prognostic information. 18F-FDG PET/CT is also used for precise delineation of the tumour volume for radiation therapy planning and dose painting, and for treatment response monitoring, by detecting residual or recurrent disease. Most of these applications would benefit from a quantitative approach to the disease, but the quantitative capability of 18F-FDG PET/CT is still underused in HNSCC. Innovations in PET/CT technology promise to overcome the issues that until now have hindered the employment of dynamic procedures in clinical practice and have limited “quantification” to the evaluation of standardized uptake values (SUV), de facto a semiquantitative parameter, the limits of which are well known to the nuclear medicine community. In this paper the principles of quantitative imaging and the related technical issues are reviewed so that professionals involved in HNSCC management can reflect on the advantages of “true” quantification. A discussion is then presented on how semiquantitative information is currently used in clinical 18F-FDG PET/CT applications in HNSCC, by discussing the improvements that could be obtained with more advanced and “personalized” quantification techniques.

Design and characterisation of a YAG(Ce) calorimeter for proton Computed Tomography application

The design and the characterization of a calorimeter system, aimed at measuring the residual energy in a proton Computed Tomography (pCT) apparatus, is described. The calorimeter has a 6 × 6 cm2 active area to fully cover the tracker area of the pCT system, being 10 cm thick it is able to stop up to 200 MeV protons and sustain 1 MHz particle rate (average rate on the whole area). The YAG(Ce) scintillator is promising for charged particle detection applications where high-count rate, good energy resolution and compact photodiode readout, not influenced by magnetic fields, are of importance. The aim of this work is to show data acquired with proton beam energy up to 175 MeV and to discuss the performances of this calorimeter.