Susanna Nuvoli

131I SPECT/CT in the Follow-up of Differentiated Thyroid Carcinoma: Incremental Value Versus Planar Imaging

Planar 131I scintigraphy is routinely used to detect radioiodine-avid metastases of differentiated thyroid carcinoma (DTC). However, the modality has limitations, such as low sensitivity and lack of anatomic landmarks. We investigated whether SPECT with integrated low-dose CT may have additional value over planar imaging in detecting residue and metastases in DTC patients. Methods: We studied 117 consecutive thyroidectomized DTC patients. On 2 different hybrid dual-head γ-cameras (55 patients on one camera and 62 on the other), 108 patients underwent 131I diagnostic imaging and SPECT/CT, and 9 underwent posttherapeutic 131I planar imaging and SPECT/CT. We assigned an incremental value to SPECT/CT when it provided better identification and interpretation of the foci of radioiodine uptake, more correct anatomic localization and characterization, and precise differentiation between tumor lesions and physiologic uptake. Results: Planar imaging showed 116 foci of uptake in 52 of 117 patients, and SPECT/CT showed 158 foci in 59 of 117 patients, confirming all foci seen on planar imaging but identifying an additional 28 occult foci in 10 of 52 patients. Fourteen occult foci were shown on SPECT/CT in 7 further patients whose planar imaging findings were negative. SPECT/CT correctly characterized 48 foci unclear on planar imaging, also defining location and extent. SPECT/CT was a determinant in classifying as neoplastic those foci for which planar imaging seemed to exclude malignancy, discriminating between residue and lymph node metastases in the neck, some of which were adjacent to salivary glands and had been missed on planar imaging. SPECT/CT also showed occult lesions in the mediastinum, abdomen, and pelvis and identified small bone metastases unsuspected on planar imaging. Globally, SPECT/CT had an incremental value over planar imaging in 67.8% of patients, modified therapeutic management in 35.6% of positive cases, and avoided unnecessary treatment in 20.3% of patients with only single benign lesions or physiologic uptake. Conclusion: 131I SPECT/CT improved planar data interpretation, showing a higher number of DTC lesions, more precisely localizing and characterizing DTC foci, and more correctly differentiating between physiologic uptake and metastases, thus permitting the most appropriate therapeutic approach to be chosen. A wider use of this method is suggested complementary to planar imaging in selected DTC patients.

Enzyme Biosensors for Biomedical Applications: Strategies for Safeguarding Analytical Performances in Biological Fluids.

Enzyme-based chemical biosensors are based on biological recognition. In order to operate, the enzymes must be available to catalyze a specific biochemical reaction and be stable under the normal operating conditions of the biosensor. Design of biosensors is based on knowledge about the target analyte, as well as the complexity of the matrix in which the analyte has to be quantified. This article reviews the problems resulting from the interaction of enzyme-based amperometric biosensors with complex biological matrices containing the target analyte(s). One of the most challenging disadvantages of amperometric enzyme-based biosensor detection is signal reduction from fouling agents and interference from chemicals present in the sample matrix. This article, therefore, investigates the principles of functioning of enzymatic biosensors, their analytical performance over time and the strategies used to optimize their performance. Moreover, the composition of biological fluids as a function of their interaction with biosensing will be presented.

The role of planar scintimammography with high-resolution dedicated breast camera in the diagnosis of primary breast cancer.

Planar scintimammography (SM) acquired with a conventional γ camera has proved a useful complementary tool to mammography (Mx) in breast cancer (BC) diagnosis, but with unsatisfactory sensitivity in small size carcinomas. In this study we assessed the role of planar SM with a high-resolution dedicated breast camera (DBC) in BC diagnosis, comparing the results with those of Mx. A consecutive series of 145 patients scheduled for biopsy for suspected BC underwent Tc-99m tetrofosmin planar SM using a newly developed DBC. Scintigraphic data were compared with Mx findings and correlated to histology. Histopathologic analysis revealed 165 lesions: 143 malignant and 22 benign. SM detected 139/143 carcinomas (overall sensitivity: 97.2%) and was true negative in 19/22 benign lesions (overall specificity: 86.4%). SM sensitivity was 91% in ≤10-mm carcinomas. SM was more accurate than Mx in 42/145 cases (29%), detecting cancer in 9 patients with Mx indeterminate for dense breasts (8/9 tumors were <10 mm), assessing additional tumor foci (all <10 mm) in 5 points with multifocal disease and correctly classifying 28 patients with inconclusive mammographic findings as affected by cancer or by benign disease. Mx was more accurate than SM in 3 patients, in each detecting 1 subcentimeter BC false negative on SM. DBC planar SM seems a highly sensitive diagnostic tool in the detection of BC, even when small in size, and in the assessment of multifocal disease. A wider employment of this procedure is thus suggested, especially in indeterminate or inconclusive mammographic findings to improve sensitivity and specificity of Mx.

99mTc-Tetrofosmin Pinhole-SPECT (P-SPECT) and Radioguided Sentinel Node (SN) Biopsy and in Breast Cancer Axillary Lymph Node Staging

We compared 99mTc-Tetrofosmin P-SPECT with radioguided SN biopsy in 101 T1/T2 BC pts to predict axillary lymph node status. The day before surgery all pts underwent lymphoscintigraphy (LS) to mark the SN, following subdermal injection of 99mTc-colloidal sulphur surrounding the breast lesion. LS was combined with pre and intraoperative gamma probe. Previously, all pts had also undergone P-SPECT. ALND was performed in all cases. The SN(s) was detected in 97/101 cases (96%) by LS and gamma probe; in the 4 missed cases P-SPECT predicted lymph node status. In the 97 comparable cases, radioguided SN biopsy showed a slightly higher accuracy than P-SPECT (94.8% vs 93.8%), but a higher false-negative rate (14.3% vs 8.6%); P-SPECT had a higher NPV (95.2% vs 92.5%). The two procedures when combined achieved 100% accuracy. Radioguided SN biopsy alone had 100% accuracy only in pts with BC < 15 mm. P-SPECT had 3 false negative cases, 2 of which were micrometastatic SNs, and 3 false positives. P-SPECT identified 81.2% of cases with a single node, determined the exact number of nodes in 82.6% of cases with 1 to 3 node and correctly classified 93.7% of pts as having < or = 3 or > 3 metastatic nodes. Radioguided SN biopsy seems indicated in selected, early stage, small BC pts, while P-SPECT shows a high sensitivity independent of primary tumor size, giving additional important preoperative prognostic information. The two procedures combined provided a better axillary lymph node status prediction in T1/T2 carcinomas, and could thus improve ALND pt selection.

Comparison of two neural network classifiers in the differential diagnosis of essential tremor and Parkinson’s disease by 123 I-FP-CIT brain SPECT

PurposeTo contribute to the differentiation of Parkinson’s disease (PD) and essential tremor (ET), we compared two different artificial neural network classifiers using 123I-FP-CIT SPECT data, a probabilistic neural network (PNN) and a classification tree (ClT).Methods123I-FP-CIT brain SPECT with semiquantitative analysis was performed in 216 patients: 89 with ET, 64 with PD with a Hoehn and Yahr (H&Y) score of ≤2 (early PD), and 63 with PD with a H&Y score of ≥2.5 (advanced PD). For each of the 1,000 experiments carried out, 108 patients were randomly selected as the PNN training set, while the remaining 108 validated the trained PNN, and the percentage of the validation data correctly classified in the three groups of patients was computed. The expected performance of an “average performance PNN” was evaluated. In analogy, for ClT 1,000 classification trees with similar structures were generated.ResultsFor PNN, the probability of correct classification in patients with early PD was 81.9±8.1% (mean±SD), in patients with advanced PD 78.9±8.1%, and in ET patients 96.6±2.6%. For ClT, the first decision rule gave a mean value for the putamen of 5.99, which resulted in a probability of correct classification of 93.5±3.4%. This means that patients with putamen values >5.99 were classified as having ET, while patients with putamen values <5.99 were classified as having PD. Furthermore, if the caudate nucleus value was higher than 6.97 patients were classified as having early PD (probability 69.8±5.3%), and if the value was <6.97 patients were classified as having advanced PD (probability 88.1%±8.8%).ConclusionThese results confirm that PNN achieved valid classification results. Furthermore, ClT provided reliable cut-off values able to differentiate ET and PD of different severities.

SPECT and PET serve as molecular imaging techniques and in vivo biomarkers for brain metastases.

Nuclear medicine techniques (single photon emission computerized tomography, SPECT, and positron emission tomography, PET) represent molecular imaging tools, able to provide in vivo biomarkers of different diseases. To investigate brain tumours and metastases many different radiopharmaceuticals imaged by SPECT and PET can be used. In this review the main and most promising radiopharmaceuticals available to detect brain metastases are reported. Furthermore the diagnostic contribution of the combination of SPECT and PET data with radiological findings (magnetic resonance imaging, MRI) is discussed.

Neuropsychophysiological findings in a case of long-standing overt ventriculomegaly (LOVA).

Long-standing overt ventriculomegaly in adults (LOVA) is a clinical entity characterized by chronic hydrocephalus with infant onset, slow evolution and clinical disturbances during adulthood. Few cases are reported in literature describing the evident contrast between the severity of hydrocephalus and the relatively spared neurological functioning and cognitive aspects. The authors describe a 59-year-old man with congenital hydrocephalus complaining of persistent gait impairment. Neurological examination showed a mild paraparesis, severe higher cortical function impairment but relatively sparing of daily living activity. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a very remarkable ventriculomegaly compressing the brain cortex but sparing the cerebellum and the brainstem. Brain Single Photon Emission Computer Tomography (SPECT) showed a prevalent cerebellar perfusion as well. Neuropsychological testing was consistent with severe cognitive deterioration and attention disorders. Language and praxis functions seemed to be preserved. Auditory oddball ERPs (P300) showed morphological abnormalities especially of late components. This case report demonstrates in vivo the level of adaptation to which human brain can reach under chronic mechanic stress conditions. The striking poor cerebral parenchyma representation and the relatively spared language and praxic abilities account for a functional reorganization of residual structures due to the neural plasticity.

123I-ioflupane brain SPECT and 123I-MIBG cardiac planar scintigraphy combined use in uncertain parkinsonian disorders

Abstract We evaluated the clinical usefulness of the combined use of 123I-ioflupane brain single photon emission computed tomography (SPECT) and 123I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy in discriminating uncertain parkinsonism with vascular lesions in striatal nuclei at magnetic resonance imaging (MRI). Forty-three consecutive patients with uncertain parkinsonism and vascular lesions at MRI in striatal nuclei were retrospectively evaluated; the uncertain differential diagnosis was between Parkinsons disease and vascular parkinsonism (PD/VP) in 22 patients, between PD and other neurodegenerative parkinsonism (PD/PS) in 11 patients and between Lewy body dementia and Alzheimer disease (LBD/AD) in the remaining 10 cases. All patients underwent 123I-ioflupane SPECT with striatal dopaminergic activity determination as binding potentials (BP; cut-off: 3.3). 123I-MIBG cardiac planar scintigraphy was performed 2 weeks later, in early (15 minutes) and delayed (240 minutes) phases also calculating heart to mediastinum (H/M) ratio (cut-off: 1.56). 123I-Ioflupane uptake was normal in 9 patients with BP values >3.3, while it was reduced in 34/43 cases with BP values <3.3 at least in one of the striatal nuclei. 123I-MIBG uptake was normal in 21/43 patients (5 of whom with normal and 16 with 123I-ioflupane striatal defects) showing the H/M ratio >1.56 in all cases; the uptake was reduced in 22/43 cases, (4 of whom were normal and 18 were with 123I-ioflupane striatal defects) with the H/M ratio <1.56 in all cases. No statistical differences were found when early and delayed H/M ratios were mutually compared. Combining the 2 radioisotopic procedures, a more reliable diagnosis was achieved in 39/43 cases properly classifying 13 PD, 10 VP, 7 PS, 5 LBD, and 4 AD. However, the diagnosis remained uncertain in four patients with normal 123I-ioflupane and reduced 123I-MIBG uptake. The results of the present study confirmed that in uncertain parkinsonian syndromes associated with vascular lesions in striatal nuclei, brain 123I-ioflupane SPECT alone did not prove able to discriminate between the different forms of disease. Only the association with 123I-MIBG cardiac scintigraphy, also with the early acquisition alone, allowed the most appropriate diagnosis in 90.7% of our cases. However, patients with normal 123I-ioflupane and reduced 123I-I-MIBG uptakes need a close clinical and instrumental follow-up as sympathetic damage could precede striatal disorders in the early stage of PD and LBD.

Cerebral and cerebellar diaschisis following carbamazepine therapy

1. The regional cerebral blood flow was studied by SPECT in patients with partial epilepsy before and after 30 days of monotherapy with carbamazepine (CBZ). 2. Both a qualitative visual interpretation and a semiquantitative analysis of SPECT was performed. All patients underwent EEG, CT scan, and MRI studies. The CBZ serum concentrations were assayed. 3. After therapy, in three patients with focal epilepsy, both a crossed cerebral and cerebellar diaschisis were observed, with respect to the side of the epileptic focus in the opposite hemisphere. No morphologic changes were detected at MRI in the cerebral or cerebellar remote hypometabolic areas found at SPECT. 4. CBZ may have a depressant action on the corticopontocerebellar pathways and on the corticocallosal connections.

The usefulness of Tc-99m-tetrofosmin SPECT/CT in the detection of residual tumors and axillary lymph node metastases in breast cancer patients following neoadjuvant therapy.

Single photon emission computed tomography (SPECT)/CT is emerging as a useful diagnostic tool in several oncological fields. In this prospective study, we assessed the usefulness of Tc-99m-tetrofosmin SPECT/CT in the detection of both residual breast tumors and axillary lymph node metastases following neoadjuvant therapy. Thirty-seven consecutive breast cancer patients scheduled to surgery following neoadjuvant therapy preoperatively underwent a Tc-99m-tetrofosmin SPECT/CT study, using a dual head gamma camera integrated with a x-ray tube for low-dose CT, including both breasts and axillary regions in the field of view. Within 1 week of SPECT/CT, all 37 patients had breast surgery with associated axillary lymph node dissection in 33/37 cases. At surgery, 31/37 patients had breast residues (microscopic in 4/31 cases and macroscopic in 27/31 cases). Axillary lymph node metastases were ascertained in 19/33 cases (N1mi: 2 cases, N1a: 8 cases, N2a: 6 cases, N2b: 3 cases). SPECT/CT sensitivity, specificity, and accuracy in detecting residual tumors were 87%, 100%, and 89.2%, respectively; the corresponding values in detecting axillary lymph node metastases were 36.8%, 92.8%, and 60.6%. SPECT/CT missed breast cancer residues in 4/31 patients, including 2 cases with microscopic residual disease. Moreover, lymph node metastases were missed in 12/19 patients (10/12 with pN1mi or pN1a metastases), all with lymph nodes with post-therapy fibrotic changes and small deposits of metastases. Tc-99m-tetrofosmin SPECT/CT proved a useful diagnostic tool in the detection and in the localization of residual breast tumors following neoadjuvant therapy. The procedure lacked in sensitivity in identifying axillary lymph node metastases, especially in patients with a limited lymph node involvement. According to our data, SPECT/CT may guide the surgeon to the most appropriate breast surgical treatment and to eventually select the most suitable axillary lymph node sampling (axillary lymph node dissection or sentinel node biopsy).