Role of dopaminergic neurotransmission in pathophysiology of action tremor in Parkinson's disease.

BACKGROUND: Rest tremor (RT), a tremor that occurs in a body part that is completely supported against gravity, is together with rigidity and bradykinesia among the core features of Parkinson's disease (PD). In addition to classical RT, many PD patients also have action tremor (AT) occurring during sustained postures or voluntary movement. Earlier studies showed a good correlation between striatal dopamine transporter (DAT) binding, measured with [(123)I] FP-CIT SPET and bradykinesia. By contrast, neither rigidity nor rest tremor seems to be closely related to the degree of dopaminergic denervation as measured by DAT imaging. Little is known about the relationship, if any, between the severity of action tremor and striatal DAT binding. SUBJECTS AND METHODS: A cross-sectional study was conducted in 94 patients (57 men and 37 women) with Parkinson's disease staging 1-2 on the Hoehn-Yahr scale. Data on the severity of action tremor and other motor signs were collected using the Unified Parkinson's Disease Rating Scale part III. DAT imaging was performed after injection of 111-185MBq of (123)I-FP-CIT. Images were visualized on Workstation Xeleris 3.0 (GE Healthcare) and reconstructed with dedicated software by a nuclear physician blinded about the clinical information of patients. Spearman correlation coefficient was performed to evaluate the relationship between putamen DAT binding and severity of bradykinesia, severity of rigidity, RT and AT respectively. Multivariable logistic regression analysis was used to assess the association between age, sex, disease duration, and levodopa equivalent daily dose and investigated variables after adjusting for possible confounders. RESULTS: In this group of patients with early PD, DAT binding in the putamen significantly correlated with the severity of bradykinesia (Spearman r=-0.35, P<0.001) but not with the severity of rigidity (Spearman r=0.02, P=0.8), RT (Spearman r=0.05, P=0.6), or AT (Spearman r=-0.03, P=0.7). The findings were confirmed by multivariable regression analysis adjusted by age, sex, disease duration, and levodopa equivalent daily dose. CONCLUSION: Our study confirms the good correlation between putamen DAT binding and bradykinesia and the lack of correlation between putamen DAT binding and rigidity/RT. In addition, we failed to found any significant correlation between putamen DAT binding and severity of action tremor, which suggests a contribution of non-dopaminergic mechanisms to its pathophysiology.

[18F-FDG PET/CT in ocular and orbital abnormalities not only neopastic: comparison with traditional imaging]. / La 18F-FDG PET/CT nello studio delle lesioni orbitarie e oculari neoplastiche e non: comparazione con l'imaging tradizionale.

UNLABELLED: Orbital and ocular neoplasms are rare tumors that could be benign or malign, primary or metastatic. Abnormalities within the orbit present a challenge in evaluation for imaging, both for morphologic examinations (ME) as weel as computed tomography (CT) and magnetic resonance (MR) and [18F]-2-deoxy-D-glucose Positron emission tomography/computed tomography (18F-FDG PET/CT). The aim of our study was evaluate 18F-FDG PET/CT role in orbital abnormalities, comparing it with CT and MR. MATERIALS AND METHODS: A retrospective analysis of 67 patients (pts) (34 males and 33 females; mean age 59.91 years old) who performed 18F-FDG PET/CT for orbital and ocular abnormalities was performed. Comparison between 18F-FDG PET/CT and ME was performed by Cohen's K also within the most representative hystologic subtypes. RESULTS: 18F-FDG PET/CT resulted positive in 19/67 pts. 47/67 pts performed ME (27/47 performed CT and 20/27 MR) within 20 days before 18F-FDG PET/CT and concordance was very poor (K=0.154). Considering 27/47 pts who performed CT, concordance was very poor (K=0.100). Considering the 20/47 pts who performed MR concordance was poor (K=0.266). Considering 19/47 pts with primary ocular NHL concordance resulted poor (K=0.269). Considering 6/47 pts with primary ocular melanoma concordance resulted very poor (K=0.182). In 9/47 pts with metastases diagnosis, concordance was absent (K=-0.189). CONCLUSIONS: CT and MR are ME that permit the evaluation of the orbital region even with limits related to the difficulties of the region. 18F-FDG PET/CT is a sensitive tecnique for several malignancies. The low concordance among 18F-FDG PET/CT and ME suggests their complementary role, then to associate 18F-FDG PET/CT even for the whole-body evaluation.

(18)F-FDG PET/CT contribution to diagnosis and treatment response of rhino-orbital-cerebral mucormycosis.

OBJECTIVE: Mucormycosis is an infection caused by mycetes mucorales, emerged as a life-threatening infection associated with severe morbidity and high mortality. Conventional imaging such as computed tomography (CT) and magnetic resonance imaging (MRI) are usually performed to assess mucormycosis extension, but they may present insufficiencies in their performance. CASE PRESENTATION: We present the case of a 13 years old patient with diagnosis of rhino-orbital-cerebral mucormycosis (RCM) who performed head MRI and [(18)F]2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) both for the infection spread assessment and for the early evaluation of response to systemic amphotericin-B treatment. CONCLUSION: This case suggests that (18)F-FDG PET/CT could be considered as a valuable tool for the initial staging of RCM when compared with MRI and should be performed as soon as possible after the first clinical suspicion of this disease. In addition (18)F-FDG PET/CT may also be useful for the assessment of response to treatment.

Comparison of (18)F-FDG PET/CT methods of analysis for predicting response to neoadjuvant chemoradiation therapy in patients with locally advanced low rectal cancer.

PURPOSE: The aim of this study was to prospectively investigate the predictive value of (18)F-FDG PET/CT semiquantitative parameters for locally advanced low rectal cancer (LARC) treated by neoadjuvant chemoradiation therapy (nCRT). METHODS: 68 patients with LARC had (18)F-FDG PET/CT scans twice (baseline and 5-6 weeks post-nCRT). All patients underwent surgery with preservation of the sphincter 8 weeks later. (18)F-FDG PET/CT analysis was performed by visual response assessment (VRA) and semiquantitative parameters: SUVmax(baseline), SUVmean(baseline), MTV(baseline), TLG(baseline), SUVmax(post-nCRT), SUVmean(post-nCRT), MTV(post-nCRT), TLG(post-nCRT); ΔSUVmax and mean and Response indexes (RImax% and RImean%). Assessment of nCRT tumor response was performed according to the Mandard's Tumor Regression Grade (TRG) and (y)pTNM staging on the surgical specimens. Concordances of VRA with TRG, and with (y)pTNM criteria were evaluated by Cohen's K. Results were compared by t student test for unpaired groups. ROC curve analysis was performed. RESULTS: VRA analysis of post-nCRT (18)F-FDG PET/CT scan for the (y)pTNM outcome showed sensitivity, specificity, accuracy, PPV, and NPV of 87.5%, 66.7%, 83.8%, 92.5%, and 53.3%, respectively. Concordances of VRA with TRG and with (y)pTNM were moderate. For the outcome variable TRG, the statistical difference between responders and non-responders was significant for SUVmax(post-nCRT) and RImean%; for the outcome variable (y)pTNM, there was a significant difference for MTV(baseline), SUVmax(post-nCRT), SUVmean(post-nCRT), MTV(post-nCRT), RImax%, and RImean%. ROC analysis showed better AUCs: for the outcome variable TRG for SUVmax(post-nCRT), SUVmean(post-nCRT), and RImean%; for the outcome variable (y)pTNM for MTVbaseline, SUVmax(post-nCRT), SUVmean(post-nCRT), MTV(post-nCRT), RImax%, and RImean%. No significant differences among parameters were found. CONCLUSIONS: Qualitative and semiquantitative evaluations for (18)F-FDG PET/CT are the optimal approach; a valid parameter for response prediction has still to be established.

Unusual 18F-FDG PET/CT finding of an oxyphil parathyroid adenoma in a patient with Hodgkin's Lymphoma / Hallazgo casual 18F-FDG PET/TC de adenoma de paratiroides oxifílico en paciente con linfoma de Hodgkin

Malignancy-associated hypercalcemia is a complication of advanced tumours that is associated to a poor prognosis. Thorough evaluation to establish its cause is essential because some patients may actually have undiagnosed primary hyperparathyroidism. We report a case of a patient affected by Hodgkin's Lymphoma and persistent hypercalcemia with an incidental 18F-FDG PET/CT finding in the anterior neck region, not ascribable to malignancy, confirmed with 99mTc-sestamibi scintigraphy. It was removed by minimally invasive surgery. It was shown to be an oxyphil parathyroid adenoma localized in an unusual site (AU)

La hipercalcemia es una complicación de tumores avanzados y se asocia a un mal pronóstico. Llevar a cabo una evaluación para establecer la causa es esencial dado que algunos pacientes oncológicos pueden presentar hipercalcemia por hiperparatiroidismo primario no diagnosticado. Se describe el caso de un paciente con linfoma de Hodgkin y con hipercalcemia persistente en el cual un estudio 18F-FDG PET/TC mostró una lesión en la región anterior del cuello, no atribuible a la neoplasia inicial, confirmada por 99mTc-sestamibi y resecada con cirugía mínimamente invasiva. Era un adenoma oxifílico de paratiroides de localización ectópica (AU)

124 Iodine: a longer-life positron emitter isotope-new opportunities in molecular imaging.

(124)Iodine ((124)I) with its 4.2 d half-life is particularly attractive for in vivo detection and quantification of longer-term biological and physiological processes; the long half-life of (124)I is especially suited for prolonged time in vivo studies of high molecular weight compounds uptake. Numerous small molecules and larger compounds like proteins and antibodies have been successfully labeled with (124)I. Advances in radionuclide production allow the effective availability of sufficient quantities of (124)I on small biomedical cyclotrons for molecular imaging purposes. Radioiodination chemistry with (124)I relies on well-established radioiodine labeling methods, which consists mainly in nucleophilic and electrophilic substitution reactions. The physical characteristics of (124)I permit taking advantages of the higher PET image quality. The availability of new molecules that may be targeted with (124)I represents one of the more interesting reasons for the attention in nuclear medicine. We aim to discuss all iodine radioisotopes application focusing on (124)I, which seems to be the most promising for its half-life, radiation emissions, and stability, allowing several applications in oncological and nononcological fields.

Prospective analysis of 18F-FDG PET/CT predictive value in patients with low rectal cancer treated with neoadjuvant chemoradiotherapy and conservative surgery.

UNLABELLED: This study prospectively assessed (18)F-FDG PET/CT in predicting the response of locally advanced low rectal cancer (LRC) to neoadjuvant chemoradiation (nCRT). METHODS: 56 patients treated with chemoradiation underwent two (18)F-FDG PET/CT scans (baseline and 5-6 weeks post-nCRT). (18)F-FDG uptake (SUVmax and SUVmean) and differences between baseline (SUV1) and post-nCRT (SUV2) scans (ΔSUV and RI%) were evaluated. Results were related to the Mandard's TRG and (y)pTNM. RESULTS: (18)F-FDG PET/CT sensitivity, specificity, accuracy, PPV and NPV resulted in 88.6%, 66.7%, 83.92%, 90.7%, and 61.5%. SUV2 resulted in better than SUV1 to predict nCRT response by TRG, with no significant statistical difference between the SUVmax2 and SUVmean2 AUC (0.737 versus 0.736; P = 0.928). The same applies to the (y)pTNM (0.798 versus 0.782; P = 0.192). In relation to the TRG, RI values had a higher AUC than ΔSUV, with no significant difference between RImax and RImean (0.672 versus 0.695; P = 0.292). The same applied to the (y)pTNM (0.742 versus 0.741; P = 0.940). In both cases ΔSUV does not appear to be a good predictive tool. Logistic regression confirmed the better predictive role of SUVmax2 for the (y)pTNM (odds ratio = 1.58) and SUVmean2 for the TRG (odds ratio = 1.87). CONCLUSIONS: (18)F-FDG PET/CT can evaluate response to nCRT in LRC, even if more studies are required to define the most significant parameter for predicting pathologic tumor changes.

Unusual ¹8F-FDG PET/CT finding of an oxyphil parathyroid adenoma in a patient with Hodgkin's Lymphoma.

Malignancy-associated hypercalcemia is a complication of advanced tumours that is associated to a poor prognosis. Thorough evaluation to establish its cause is essential because some patients may actually have undiagnosed primary hyperparathyroidism. We report a case of a patient affected by Hodgkin's Lymphoma and persistent hypercalcemia with an incidental (18)F-FDG PET/CT finding in the anterior neck region, not ascribable to malignancy, confirmed with (99m)Tc-sestamibi scintigraphy. It was removed by minimally invasive surgery. It was shown to be an oxyphil parathyroid adenoma localized in an unusual site.

Useful diagnostic biometabolic data obtained by PET/CT and MR fusion imaging using open source software.

In the last decade numerous attempts were considered to co-register and integrate different imaging data. Like PET/CT the integration of PET to MR showed great interest. PET/MR scanners are recently tested on different distrectual or systemic pathologies. Unfortunately PET/MR scanners are expensive and diagnostic protocols are still under studies and investigations. Nuclear Medicine imaging highlights functional and biometabolic information but has poor anatomic details. The aim of this study is to integrate MR and PET data to produce distrectual or whole body fused images acquired from different scanners even in different days. We propose an offline method to fuse PET with MR data using an open-source software that has to be inexpensive, reproducible and capable to exchange data over the network. We also evaluate global quality, alignment quality, and diagnostic confidence of fused PET-MR images. We selected PET/CT studies performed in our Nuclear Medicine unit, MR studies provided by patients on DICOM CD media or network received. We used Osirix 5.7 open source version. We aligned CT slices with the first MR slice, pointed and marked for co-registration using MR-T1 sequence and CT as reference and fused with PET to produce a PET-MR image. A total of 100 PET/CT studies were fused with the following MR studies: 20 head, 15 thorax, 24 abdomen, 31 pelvis, 10 whole body. An interval of no more than 15 days between PET and MR was the inclusion criteria. PET/CT, MR and fused studies were evaluated by two experienced radiologist and two experienced nuclear medicine physicians. Each one filled a five point based evaluation scoring scheme based on image quality, image artifacts, segmentation errors, fusion misalignment and diagnostic confidence. Our fusion method showed best results for head, thorax and pelvic districts in terms of global quality, alignment quality and diagnostic confidence,while for the abdomen and pelvis alignement quality and global quality resulted poor due to internal organs filling variation and time shifting beetwen examinations. PET/CT images with time of flight reconstruction and real attenuation correction were combined with anatomical detailed MRI images. We used Osirix, an image processing Open Source Software dedicated to DICOM images. No additional costs, to buy and upgrade proprietary software are required for combining data. No high technology or very expensive PET/MR scanner, that requires dedicated shielded room spaces and personnel to be employed or to be trained, are needed. Our method allows to share patient PET/MR fused data with different medical staff using dedicated networks. The proposed method may be applied to every MR sequence (MR-DWI and MR-STIR, magnet enhanced sequences) to characterize soft tissue alterations and improve discrimination diseases. It can be applied not only to PET with MR but virtually to every DICOM study.

Radiometabolic treatment of bone-metastasizing cancer: from 186rhenium to 223radium.

Skeletal metastases occur in many patients with different kinds of malignant tumors, especially in advance stage of breast cancer (in 47%-85% of patients), prostate cancer (33-85%), and lung cancer (32%-60%). The management of painful skeletal metastases is complicated and should be carried out by a multidisciplinary approach including conventional analgesics, antitumor therapy (chemo- and hormone therapy), osteoclast-inhibitory agents (bisphosphonates), corticosteroids, external-beam radiotherapy, surgery, and nuclear medicine therapy. The nuclear medicine therapy for palliation of pain from bone metastases is a systemic radionuclide therapy based on the use of radiopharmaceuticals. In several studies the efficacy of bone-seeking radiopharmaceuticals have been demonstrated in terms of pain reduction from diffuse skeletal metastases. In this review, we will summarize the current literature on bone-seeking radiopharmaceuticals for the treatment of painful bone metastases (Phosphorus-32, Strontium-89, Rhenium-186, Rhenium-188, Samarium-153, and Radium-223) and the combination therapy with biphosphonates and chemotherapy.

[Correlation between cognitive impairment and plasma levels of clusterin/ApoJ in Parkinson disease patients not affected by dementia]. / Correlazione tra deterioramento cognitivo e livello plasmatico della clusterina/ApoJ in pazienti con malattia di Parkinson non affetti da demenza.

Cognitive impairment is frequent in patients with Parkinson's disease (PD), and can range from mild deterioration to dementia. Recently a contribution of Alzheimer's disease for the cognitive dysfunction in PD has been proposed, whereas the presence of tau protein and amyloid was recognized. Clusterin/ApoJ is a protein involved in the deposition of beta-amyloid and in its neurotoxicity. In this study we aimed to investigate the clusterin/ApoJ's plasma levels in patients with PD to assess its potential role in fisiopathogenetic cognitive impairment.

[Unusual sentinel lymph nodes detected by lymphoscintigraphy in cutaneous melanoma patients]. / Linfonodi sentinella "inusuali" alla linfoscintigrafia in pazienti con melanoma cutaneo.

Lymphoscintigraphy and radio-guided research of the sentinel lymph node is the most important investigation in the staging of patients with cutaneous melanoma, because it allows the identification of the lymphatic drainage pathways, not always predictable, and locate the sentinel node in classic basins and in "unexpected" regions. The aim of this study was to evaluate the incidence of cases of unusual sentinel nodes detected by lymphoscintigraphy and their prognostic significance in patients with cutaneous melanoma.

[Lung perfusion scintigraphy in pediatric patients with congenital malformations]. / La scintigrafia polmonare in età neonatale e pediatrica per patologie congenite.

Congenital malformations are an heterogeneous group of disorders that can lead changes in pulmonary perfusion and then can be evaluated with lung perfusion scintigraphy. We selected five patients in which the role of lung perfusion scintigraphy emerges as a reliable and non-invasive imaging technique. Lung perfusion scintigraphy is a useful tool in pediatric patients with congenital malformations allowing an accurate evaluation of the best therapeutic strategy and its results.

[18F-FDG PET/CT in a patient with clinical suspicion of giant cell arteritis]. / La gestione di un caso di arterite a cellule giganti con la 18F-FDG PET/TC.

We report the case of a 72 year old man with clinical suspicion of giant cell arteritis (GCA); in this case 18F-FDG PET/CT has been useful from the diagnosis to the control of the response to therapy. He performed the first 18F-FDG PET/CT that showed increased uptake of 18F-FDG in the aortic arch, brachial artery, common iliac and femoral arteries and in the temporal cerebral sites bilaterally. The patient then began a cortisonic therapy that led straight to the improvement of clinical symptoms, and repeated 18F-FDG PET/CT 3 months later the beginning of therapy that showed reduced uptake in the same sites of the first 18F-FDG PET/CT. This patient continued the cortisonic therapy, progressively reducing it until the definitive ending.

18F-FDG PET/CT in suspected recurrences of epithelial malignant pleural mesothelioma in asbestos-fibers-exposed patients (comparison to standard diagnostic follow-up).

This retrospective study evaluated the role of 18-fluorine-labeled 2-deoxy-2-fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with previous occupational or environmental exposure to asbestos, with histopathological diagnosis of epithelial malignant pleural mesothelioma and suspected recurrences, comparing the data from 18F-FDG PET/CT and computed tomography with contrast enhancement (CECT). 18F-FDG PET/CT has greater sensitivity than CECT in identifying local extent, lymph nodes, and metastasis. 18F-FDG PET/CT whole-body explorations are useful to monitor the follow-up and evaluate the metabolic response to chemo- and radiotherapy, modifying the scheduled treatment plan.

[The PET/CT with 18F-fluorocholine in the diagnosis of gliomatosis cerebri type 2]. / La tomografia a emissione di positroni con 18F-fluorocolina nella gliomatosi cerebrale di tipo II.

In a patient with cerebral gliomatosis type II MRI revealed a large area of altered signal in the temporal region, parietal and occipital lobes associated with a single nodule with perilesional contrast enhancement, which showed increased uptake on PET/CT with 18F-FCH, characterizing heterogeneous cellularity of the tumor.

[Relapse of primary testicular non-Hodgkin's lymphoma detected by 18F-FDG-PET/CT]. / Recidiva muscolo-cutanea di linfoma non-Hodgkin primitivo del testicolo riconosciuta con 18F-FDG-PET/TC.

We report the case of a 62-year-old male with a history of primary testicular non-Hodgkin's lymphoma, treated with orchidectomy. After 14 months, the patient developed left leg swelling and pain, and was diagnosed and treated as having leg vein thrombosis. 18F-FDG-PET/CT showed a relapse of testicular lymphoma in the cutaneous muscle tissue of the left leg.

[Distribution of 18F-FDG in a patient with evolving abdominal aortic aneurysm]. / Captazione del 18F-FDG in un grave caso di aneurisma dell'aorta addominale in evoluzione.

We report the case of a patient with abdominal aortic aneurysm who underwent serial 18F-FDG PET/CT examinations to evaluate the risk of rupture and to guide appropriate surgical or medical management.

[Role of imaging techniques in the evaluation of chyluria]. / Chiluria notturna: ruolo della diagnostica per immagini.

Lymphoscintigraphy is a first-line imaging technique for the assessment of abnormal lymphatic drainage in chyluria. It can provide information about the site of origin of chyluria, and may be helpful in selecting patients for surgery and assessing treatment efficacy. We report the case of a 59-year-old male with chyluria correctly diagnosed with lymphoscintigraphy.

[Peritoneal carcinomatosis from ovarian cancer: role of 18F-FDG-PET/CT and CA125]. / La carcinosi peritoneale da carcinoma ovarico: utilità della 18F-FDG-PET/TC e del biomarker CA125.

The purpose of this study was to evaluate the contribution of 18F-FDG-PET/CT in highlighting the peritoneal involvement in patients with ovarian cancer, also in relation to the biomarker CA125. We retrospectively analyzed 64 female patients with histological diagnosis of ovarian cancer who underwent 18F-FDG-PET/CT and CA125 measurement. Sensitivity and specificity of 18F-FDG-PET/CT were both 90.63% (95% CI: 80-100%). Sensitivity and specificity of CA125 were 93.33% (95% CI: 80-100%) and 33.33% (95% CI: 25-64%), respectively. In patients with peritoneal carcinomatosis from ovarian cancer, it is recommended to perform 18F-FDG-PET/CT, in particular when elevated CA125 levels are detected.