A kinetics-based approach to amyloid PET semi-quantification.

PURPOSE: To develop and validate a semi-quantification method (time-delayed ratio, TDr) applied to amyloid PET scans, based on tracer kinetics information. METHODS: The TDr method requires two static scans per subject: one early (~ 0-10 min after the injection) and one late (typically 50-70 min or 90-100 min after the injection, depending on the tracer). High perfusion regions are delineated on the early scan and applied onto the late scan. A SUVr-like ratio is calculated between the average intensities in the high perfusion regions and the late scan hotspot. TDr was applied to a naturalistic multicenter dataset of 143 subjects acquired with [18F]florbetapir. TDr values are compared to visual evaluation, cortical-cerebellar SUVr, and to the geometrical semi-quantification method ELBA. All three methods are gauged versus the heterogeneity of the dataset. RESULTS: TDr shows excellent agreement with respect to the binary visual assessment (AUC = 0.99) and significantly correlates with both validated semi-quantification methods, reaching a Pearson correlation coefficient of 0.86 with respect to ELBA. CONCLUSIONS: TDr is an alternative approach to previously validated ones (SUVr and ELBA). It requires minimal image processing; it is independent on predefined regions of interest and does not require MR registration. Besides, it takes advantage on the availability of early scans which are becoming common practice while imposing a negligible added patient discomfort.

Italian consensus recommendations for a biomarker-based aetiological diagnosis in mild cognitive impairment patients.

BACKGROUND AND PURPOSE: Biomarkers support the aetiological diagnosis of neurocognitive disorders in vivo. Incomplete evidence is available to drive clinical decisions; available diagnostic algorithms are generic and not very helpful in clinical practice. The aim was to develop a biomarker-based diagnostic algorithm for mild cognitive impairment patients, leveraging on knowledge from recognized national experts. METHODS: With a Delphi procedure, experienced clinicians making variable use of biomarkers in clinical practice and representing five Italian scientific societies (neurology - Società Italiana di Neurologia per le Demenze; neuroradiology - Associazione Italiana di Neuroradiologia; biochemistry - Società Italiana di Biochimica Clinica; psychogeriatrics - Associazione Italiana di Psicogeriatria; nuclear medicine - Associazione Italiana di Medicina Nucleare) defined the theoretical framework, relevant literature, the diagnostic issues to be addressed and the diagnostic algorithm. An N-1 majority defined consensus achievement. RESULTS: The panellists chose the 2011 National Institute on Aging and Alzheimer's Association diagnostic criteria as the reference theoretical framework and defined the algorithm in seven Delphi rounds. The algorithm includes baseline clinical and cognitive assessment, blood examination, and magnetic resonance imaging with exclusionary and inclusionary roles; dopamine transporter single-photon emission computed tomography (if no/unclear parkinsonism) or metaiodobenzylguanidine cardiac scintigraphy for suspected dementia with Lewy bodies with clear parkinsonism (round VII, votes (yes-no-abstained): 3-1-1); 18 F-fluorodeoxyglucose positron emission tomography for suspected frontotemporal lobar degeneration and low diagnostic confidence of Alzheimer's disease (round VII, 4-0-1); cerebrospinal fluid for suspected Alzheimer's disease (round IV, 4-1-0); and amyloid positron emission tomography if cerebrospinal fluid was not possible/accepted (round V, 4-1-0) or inconclusive (round VI, 5-0-0). CONCLUSIONS: These consensus recommendations can guide clinicians in the biomarker-based aetiological diagnosis of mild cognitive impairment, whilst guidelines cannot be defined with evidence-to-decision procedures due to incomplete evidence.

Semi-quantification and grading of amyloid PET: A project of the European Alzheimer's Disease Consortium (EADC).

BACKGROUND: amyloid-PET reading has been classically implemented as a binary assessment, although the clinical experience has shown that the number of borderline cases is non negligible not only in epidemiological studies of asymptomatic subjects but also in naturalistic groups of symptomatic patients attending memory clinics. In this work we develop a model to compare and integrate visual reading with two independent semi-quantification methods in order to obtain a tracer-independent multi-parametric evaluation. METHODS: We retrospectively enrolled three cohorts of cognitively impaired patients submitted to 18F-florbetaben (53 subjects), 18F-flutemetamol (62 subjects), 18F-florbetapir (60 subjects) PET/CT respectively, in 6 European centres belonging to the EADC. The 175 scans were visually classified as positive/negative following approved criteria and further classified with a 5-step grading as negative, mild negative, borderline, mild positive, positive by 5 independent readers, blind to clinical data. Scan quality was also visually assessed and recorded. Semi-quantification was based on two quantifiers: the standardized uptake value (SUVr) and the ELBA method. We used a sigmoid model to relate the grading with the quantifiers. We measured the readers accord and inconsistencies in the visual assessment as well as the relationship between discrepancies on the grading and semi-quantifications. CONCLUSION: It is possible to construct a map between different tracers and different quantification methods without resorting to ad-hoc acquired cases. We used a 5-level visual scale which, together with a mathematical model, delivered cut-offs and transition regions on tracers that are (largely) independent from the population. All fluorinated tracers appeared to have the same contrast and discrimination ability with respect to the negative-to-positive grading. We validated the integration of both visual reading and different quantifiers in a more robust framework thus bridging the gap between a binary and a user-independent continuous scale.

Use of the BasGan algorithm for [123I]FP-CIT SPECT quantification: a phantom study.

AIM: The BasGan algorithm has been specifically developed for semi-automatic quantification of [123I]FP-CIT SPECT studies. The aim of this work was to evaluate the software linearity and its dependence on the main acquisition parameters of the SPECT study. METHODS: The anthropomorphic Striatal Phantom filled with different striatal to background activity concentration ratios was used to verify software linearity. The software response was studied with different acquisition parameters and system configurations. For this purpose, phantom studies were performed with varying radius of rotation, pixel size, number of projections and with different collimator types. For each configuration the tomographic spatial resolution was also determined using the Triple Line Source Phantom. The reconstructed SPECT images were corrected for attenuation and scatter. RESULTS: The BasGan outcome highly correlates with the real Specific Binding Ratio when fixed gamma camera configuration and reconstruction method are used. However, the software quantification depends on system configuration and decreases with increasing partial volume effect. A comparison of the BasGan output with tomographic spatial resolution data for each configuration shows that the software response highly correlates with this quantity. CONCLUSION: The BasGan algorithm is a free, easy-to-use and solid tool for quantification of [123I]FP-CIT images. The software outcome depends on system configuration, but highly correlates with tomographic spatial resolution. Then, the measurement of this quantity turns out to be a simple method to normalize the BasGan quantification for different imaging devices, making it possible the use of available reference values for normal subjects and multicentre studies.

Evaluation of patients with coronary artery disease. IQ-SPECT protocol in myocardial perfusion imaging: Preliminary results.

UNLABELLED: Quantification of myocardial perfusion scintigraphy is often performed to assist physicians in detecting coronary artery disease (CAD). Modern software and hardware packages provide improvements able to shorten scan time and/or reduce administered activity, without compromising image quality in radionuclide myocardial perfusion imaging (MPI). Recently, multifocal collimators were introduced with dedicated reconstruction software, named IQ-SPECT, able to shorten considerably scan time. The aim of our study was to compare this new protocol to the already validated standard ones. PATIENTS, METHODS: We enrolled 43 patients with suspected or diagnosed CAD. All patients underwent a two-days protocol radionuclide myocardial perfusion scan at rest and after a standard stress test (exercise or dipyridamole) after administering 99mTc-tetrofosmin. Images were acquired on a 2-head gamma camera and reconstructed with attenuation correction. All the images were scored using a 17-segments model by three experienced physicians, blind to clinical data and to acquisition and processing modality. RESULTS, CONCLUSION: No significant differences were recorded in perfusion scores on paired t-test and Wilcoxon among the full-time images reconstructed with standard protocol or IQ-SPECT, both overall on a 17-segments evaluation and when considering different territories of distribution. MPI with IQ-SPECT protocol can be acquired at about a quarter scan time without disagreement compared to full time scan acquisition performed with standard protocols.

The relationship between cerebral vascular disease and parkinsonism: The VADO study.

BACKGROUND: The observation of gait abnormalities, parkinsonism and vascular lesions in elderly patients is often reported as vascular parkinsonism (VP). However the status of striatal dopamine transporter (DAT) and the effects of brain vascular lesions on motor features and levodopa responsiveness are poorly defined. METHODS: We recorded clinical features, chronic response to levodopa and vascular risk factors in a cross-sectional cohort of consecutive elderly patients with possible Parkinson's disease (PD) or VP recruited in 20 centers in Italy. RESULTS: We included a total of 158 patients. Onset of motor symptoms was asymmetric in 93 (59%) and symmetric in 65 patients (41%). Symmetric motor onset was associated with greater disease severity. Chronic levodopa response was positive in 75 (47.8%) and negative in 82 patients (52.2%). A negative response to levodopa was associated with greater frequency of symmetric onset of motor symptoms, worst disease severity, absence of dyskinesia and greater number of vascular risk factors. Frontal lobe showed largest vascular load. Striatal DAT was normal in 48 (30.4%) and abnormal in 110 (69.6%) patients. Patients with normal DAT binding showed higher vascular load at MRI. Significant predictive factors of worst disease severity and negative response to levodopa were hypertension, vascular lesions in basal ganglia/periventricular regions, and normal DAT uptake. CONCLUSIONS: Multiple cerebral vascular lesions modify clinical presentation and severity in patients with parkinsonism and this is underlined by specific risk factors primarily hypertension. Striatal DAT assessment is helpful in identifying patients where therapy benefit is less likely.

Desarrollo de un sistema de educación a distancia en el sector público de salud: 2004-2009 / Development of a distance education program in the Public Health System in Chile, 2004-2009

This paper reports the gradual development and results achieved in the distance education program set up in the Public Health System in Chile in 2004. Up to date, more than 22,000 students from 29 different health divisions have been trained. This strategy was designed to provide more flexibility and diversity to the training programs of the Health System within the framework of a deep and complex organizational change promoted by Health Reform. The main results show that the integration of organizational, teaching, logistic and budgetary aspects has turned out to be a key element in its success, validating the relevance of the provided solutions. The access to training by means of e-learning or blended learning (electronic education that includes traditional and distance learning activities) allowed employees to choose more independently what, where and when to study. This fact accounts for the high demand for this program. Through this initiative, the National Health System, introduced a wider scope of responses to training needs, which will mean a better adaptation to the challenges associated to health care.

[Development of a distance education program in the public health system in Chile, 2004-2009]. / Desarrollo de un sistema de educación a distancia en el sector público de salud: 2004-2009.

This paper reports the gradual development and results achieved in the distance education program set up in the Public Health System in Chile in 2004. Up to date, more than 22,000 students from 29 different health divisions have been trained. This strategy was designed to provide more flexibility and diversity to the training programs of the Health System within the framework of a deep and complex organizational change promoted by Health Reform. The main results show that the integration of organizational, teaching, logistic and budgetary aspects has turned out to be a key element in its success, validating the relevance of the provided solutions. The access to training by means of e-learning or blended learning (electronic education that includes traditional and distance learning activities) allowed employees to choose more independently what, where and when to study. This fact accounts for the high demand for this program. Through this initiative, the National Health System, introduced a wider scope of responses to training needs, which will mean a better adaptation to the challenges associated to health care.

Functional compensation in incipient Alzheimer's disease.

Aim of this study was to investigate the functional compensation mechanism in incipient Alzheimer's disease (AD). Seventeen elderly healthy subjects and nine amnestic MCI patients with incipient AD underwent brain MR scan and 99mTc ECD SPECT. We processed all images with SPM2, we created t maps, showing the wholebrain GM atrophy and functional changes, and we properly masked them with each other in order to assess relatively preserved perfusion or depression. Incipient AD showed GM atrophy in the medial temporal and temporoparietal lobes, in the insula and in the retrosplenial cortex, and GM hypoperfusion in the medial temporal and temporoparietal lobes. Relatively preserved perfusion, we could hypothesize to be compensatory in the setting of neuronal loss, was found in the posterior cingulate, in the head of the hippocampus, in the amigdala, and in the insula bilaterally, while functional depression occurred in bilateral parahippocampal gyri. In AD, a perfusional compensatory mechanism takes place in the neocortex, while perfusional depression occurs in the medial temporal lobe. These results help understand the reactive phenomena induced by the brain to try and counteract the pathological changes of AD.

Clinical and histopathological risk factors to predict sentinel lymph node positivity, disease-free and overall survival in clinical stages I-II AJCC skin melanoma: outcome analysis from a single-institution prospectively collected database.

BACKGROUND: To investigate if the tumour infiltrating lymphocytes (TILs) are able to predict the sentinel lymph node (SLN) positivity, the disease-free survival (DFS) and overall survival (OS) in clinical stages I-II AJCC primary cutaneous melanoma (PCM). METHODS: The study included consecutive patients with PCM, all diagnosed, treated and followed up prospectively. Logistic regression was used to investigate the association between DFS, OS, SLN positivity and Breslow thickness, Clark level, TIL, ulceration, lesion site, gender, regression and age. RESULTS: From November 1998 to October 2008, 1251 consecutive patients with PCM were evaluated. Median age was 51 (range 15-96) with 32.2% (N=393) of them older than 60; 44.8% of them were males. Of the whole series, a total of 404 patients with primary vertical growth phase (VGP) melanoma and no clinical evidence of metastatic disease underwent SLN biopsy. Of these, 74 (18.8%) had a positive SLN. In a multivariate analysis, primary melanoma on the extremities versus that on the axial locations (truncal and head/neck) (OR 0.49, 95% CI 0.25-0.98, p 0.04) and TILs (TILs versus no TILs) (OR 0.47, 95%CI 0.25-0.90, p 0.02) were predictive for lower probability of SLN involvement, while thickness (>4mm versus 0-1mm) (OR 24, 19, 95% CI 4.91-119.13, p<.001) was predictive for higher risk of SLN positivity. A multivariate stepwise analysis confirmed these results. The histological status of the SLN was the most significant predictor of DFS and OS. Patients with a negative SLN had a 5-year DFS of 75.9%, compared with 35.2% in patients with a positive SLN (p<.0001) and a 5-year OS of 88.7% versus 42.9%, respectively (p<.0001). CONCLUSIONS: Our study demonstrates that the absence of TILs predicts SLN metastasis, in multivariate analysis the SLN positivity predicts DFS and OS.

Late-onset sporadic ataxia, pontine lesion, and retroperitoneal fibrosis: a case of Erdheim-Chester disease.

A 60-year-old man with progressive gait ataxia and mild pyramidal signs showed at MRI a pontine lesion with post-contrast enhancement in the left middle cerebellar peduncle. Diagnosis of Erdheim-Chester disease (ECD), a rare non-Langerhans cell histiocytosis, was suggested, further supported by a previously diagnosed retroperitoneal fibrosis. X-ray films demonstrated characteristic bilateral and symmetric osteosclerosis of the long bones of the lower limbs, which at radionuclide studies exhibited a marked increase in technetium-99 uptake. A cerebral 18FDG-PET showed a relevant pontine uptake of the tracer. Re-evaluation of a past retroperitoneal biopsy showed an intense CD68+, CD1a-, and S100- infiltrate of histiocytes with foamy cytoplasm, thus confirming the diagnosis. ECD should be regarded as a rare cause of adult-onset sporadic ataxia, especially when pontine lesions and extraneurological manifestations are present.

Cerebral perfusion correlates of conversion to Alzheimer's disease in amnestic mild cognitive impairment.

OBJECTIVE: Aim of this study was to find cerebral perfusion correlates of conversion to dementia in patients with amnestic MCI. METHODS: 17 healthy subjects (age = 69 +/- 3, 9 females), and 23 amnestic MCI patients (age = 70 +/- 6, 10 females) underwent brain MR scan and (99m)Tc ECD SPECT. Conversion to AD was ascertained on average 19 +/- 10 months after baseline: 9 had converted (age = 69 +/- 3, 4 females), and 14 had not (age = 71 +/- 8, 6 females). We processed SPECT images with SPM2 following an optimized protocol and performed a voxel-based statistical analysis comparing amnestic MCI patients converted to AD and non-converted to dementia vs controls. We assessed the effect of gray matter atrophy on the above results with SPM2 using an optimized Voxel-Based Morphometry (VBM) protocol. We compared significant hypoperfusion with significant atrophy on a voxel-byvoxel basis. RESULTS: In comparison with normal controls, amnestic MCI patients who converted to AD showed hypoperfusion in the right parahippocampal gyrus and left inferior temporal and fusiform gyri,whereas those who did not convert showed hypoperfusion in the retrosplenial cortex, precuneus and occipital gyri, mainly on the left side. We found no overlap between significant atrophy and significant hypoperfusion regions. CONCLUSIONS: Parahippocampal and inferior temporal hypoperfusion in amnestic MCI patients appears as a correlate of conversion to AD; hypoperfusion in the retrosplenial cortex is involved in memory impairment but does not seem the key prognostic indicator of conversion to dementia.

Sentinel node biopsy in the surgical management of breast cancer: experience in a general hospital with a dedicated surgical team.

The aims of this study were to analyse the feasibility and accuracy of the sentinel lymph node biopsy (SLNB) procedure as performed in a general hospital compared with the literature results; to report on the organizational aspects of planning surgical time with higher accuracy of pathological analysis; and to verify that there is a real advantage of SLNB in the surgical management of breast cancer. From October 1999 to September 2000, 371 consecutive patients with T1-2N0 breast lesions underwent SLNB. The immunoscintigraphic method of sentinel node identification was the main one used, the blue dye method being used only when the lymphoscintigraphic method was unsuccessful in identifying sentinel nodes. SLNB was done under either general or local anaesthesia, depending on how the surgical procedure was organized and clinically planned. SLNB was successful in 99% of these T1-2N0 breast cancer cases, and in 71% no metastases were found in the sentinel node. In 47% of cases with axillary metastasis only the sentinel node was involved. Nodal involvement was not present in any case of microinvasive or in situ carcinoma. In T1 cancers nodal involvement was present in 21%; in T2 cases the corresponding rate reached 51%. The results obtained with the SLNB procedure at Bergamo Hospital are similar to the literature data. When a dedicated surgical team, the nuclear medicine department and the pathology department work together, a general hospital can provide breast cancer patients with appropriate surgical treatment.

Changes in regional cerebral blood flow after a cold hand test in systemic lupus erythematosus patients with Raynaud's syndrome.

The appearance of vasospastic features in the central nervous system (CNS) after a cold stressor test was Investigated through single photon emission computed tomography (SPECT) of regional cerebral blood flow in patients with systemic lupus erythematosus, with and without Raynaud's syndrome, and in scleroderma patients. We have shown that Raynaud's syndrome may occur in the CNS and that anticardiolipin or lupus anticoagulant positivity may favour perfusion defects.

Gated Tc-99m sestamibi SPECT versus stress-rest SPECT in detecting coronary artery disease: correlation with coronary angiography in patients without myocardial infarction.

PURPOSE: It is possible to simultaneously evaluate wall thickening and perfusion abnormalities with radionuclide techniques that use tracers such as Tc-99m MIBI. We presumed that detection of wall thickening by gated MIBI SPECT imaging in the presence of a stress-induced perfusion defect correlates with reversibility of that defect on resting images. Therefore, the aim of our study was to analyze, in patients without myocardial infarction, resting wall thickening and stress perfusion imaging as an alternative to conventional stress-rest imaging. METHODS AND RESULTS: The patients (n = 44) underwent an exercise (n = 37) or pharmacologic (n = 7) stress protocol. All patients had previous coronary angiography within 3 months. Stress-rest MIBI SPECT and gated MIBI SPECT studies were analyzed by visual scoring. The sensitivity and specificity of segmental analysis of both stress-rest MIBI SPECT perfusion and gated MIBI SPECT studies for the overall detection of coronary artery disease were, respectively, 71% and 96%. For patient evaluation for detection of coronary artery disease, stress-rest MIBI SPECT perfusion and gated MIBI SPECT studies showed a sensitivity rate of 96% for both and specificity rates of 84% and 79%, respectively. CONCLUSIONS: Our data revealed close agreement between reversible perfusion defects on stress-rest MIBI SPECT scans and significant wall thickening on gated MIBI SPECT stress images in patients without previous myocardial infarction (95%). Gated MIBI SPECT stress, without resting studies, which provide an assessment of wall motion and wall thickening, potentially allows stress defect reversibility to be evaluated in patients without previous myocardial infarction.

Cold lesion of a vertebral angioma with Tc-99m-labeled monoclonal antibodies against granulocytes.

Antigranulocyte immunoscintigraphy is indicated for diagnostic imaging to determine the location and extent of infection. We present a case of a focal cold lesion in a vertebra of a patient thought to have a septic focal lesion. Whole-body scanning and dorsal spine SPECT revealed no focal increased uptake. CT and MR studies revealed the presence of a vertebral angioma. Conditions associated with a defect of uptake in immunoscintigraphy are discussed.

Renal SPECT with Tc-99m DMSA in children with upper urinary tract infections using a triple-headed gamma camera.

UNLABELLED: Renal cortical scintigraphy with Tc-99m DMSA provides an excellent imaging modality for the assessment of cortical damage secondary to upper urinary tract infection (UTI). METHODS: The authors evaluated 48 children with UTI, 12 of whom had a history of vescico-ureteral reflux (from first of fourth degree), by planar scintigraphy and SPECT using a triple-headed gamma camera equipped with parallel-hole, high-resolution collimators. RESULTS: SPECT images yielded positive findings in 36 kidneys, whereas planar scans yielded positive findings in 18 kidneys. The total number of lesions detected by SPECT was 51, whereas the number found with the planar technique was 23. CONCLUSION: This study demonstrates the superiority of SPECT scanning in detecting kidney lesions in children with UTI.