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.

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.

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.

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.

Feasibility of simultaneous Tc99m sestamibi and 2D-echo cardiac imaging during dobutamine pharmacologic stress. Preliminary results in a female population.

Feasibility of simultaneous 2D-Echo and SPECT Tc99m Sestamibi imaging during dobutamine infusion was evaluated in a female population with suspected coronary artery disease and scheduled for diagnostic coronary angiography. A total of 49 consecutive subjects were studied. Patients under continuous ECG and 2D-Echo monitoring underwent standard dobutamine infusion at increasing doses to a diagnostic end-point. Tc99m Sestamibi was administered at the peak of the dobutamine effect. With this approach, 35 patients were identified correctly by 2D-Echo (Sensitivity = 60.1%; Specificity = 83.3%; Agreement = 71.4%; k = 0.43). Perfusion imaging with Tc99m Sestamibi resulted in correctly identifying 41 patients (Sensitivity = 83%; Specificity = 84%; Agreement = 83.6%; k = 0.67). Combining information obtained from the two tests resulted in increased specificity (92%) and decreased sensitivity (64%). Simultaneous assessment of perfusion and function with Tc99m Sestamibi and 2D-Echo imaging during dobutamine administration is easily performed without added risk or discomfort to the patient. Tc99m Sestamibi appeared to be slightly superior to 2D-Echo for the detection of CAD in this population, but the difference does not reach conventional statistical significance. The combined use of the two independent tests did not substantially improve the diagnostic accuracy of each method.

An unusual adrenal metastasis secondary to Hürthle cell carcinoma of the thyroid.

A 66-year-old woman with Hürthle cell thyroid carcinoma associated with a right adrenal gland metastasis suspected on a postradioiodine therapy scan, is reported. Histology specimens confirmed the suspicion. Adrenal metastases have never been reported previously in this kind of tumor. On radionuclide imaging, there was marked I-131 uptake in the tumor remnant and its metastases, and the tumor spread through both lymphatic and hematogenous routes, as shown by lymph node, bone, and lung metastases.

Longitudinal evaluation of prostate-specific antigen levels in a case-control study.

BACKGROUND: Over the last period--late 1970 to early 1990--the incidence of prostate carcinoma has nearly doubled, even though many more patients die with prostate cancer rather than of it. This finding, together with the slow growth of this tumor and the absence of a controlled trial, makes early diagnosis for this pathology quite questionable. On the other hand, it is well known that prostatic carcinoma is curable as long as it is intracapsular and that there is an ever increasing encouragement for early detection in all diseases. Since prostatic pathology increases its incidence as age advances, the first step in early diagnosis is to be able to discriminate between healthy, benign prostatic hyperplasia and cancer cases with a well-accepted and easily understandable method. The problem is to find the best method to do it. METHODS: We measured serum prostate-specific antigen (PSA) levels in 435 men participating in an epidemiological study, at first in 1987 and again in 1992. Men with PSA levels above 4 ng/ml (in 1992) were invited to undergo other diagnostic tests (digital rectal examination, transrectal ultrasonography, biopsy) in sequence on the basis of the results of the previous tests. The pathological findings from biopsies were the reference test to determine the presence or absence of prostate cancer (2.5% of the population). RESULTS: We divided PSA concentrations into three categories, according to the most used cutoffs ( < 4, 4-10, > 10 ng/ml); in the meantime, we took into account the change rate in PSA concentration in time, defined as delta PSA. By the comparison between PSA categories and delta PSA, we found out that the first one does not discriminate between benign and malignant pathologies, while the use of delta PSA strongly discriminates them (p < 0.001). CONCLUSION: On the basis of our results, we think that delta PSA might be the best parameter to indicate the presence of prostate cancer cases in an asymptomatic population.

Is serum PSA measurement a good test for early diagnosis of prostate cancer? Results of a pilot study and cost analysis.

Over the last years--late 1970s to early 1990s--the incidence of prostate carcinoma has nearly doubled, even though many more patients die suffering from prostate cancer than because of it. This finding, together with the slow growth of this tumor and the absence of a controlled trial that would suggest a benefit from screening, makes early diagnosis of this disease quite questionable. On the other hand, it is well known that prostatic carcinoma is curable as long as it is intracapsular, and that there is an ever increasing encouragement to early detection in all diseases. The costs of screening and the difficulty in balancing the benefits of screening against its negative effects, such as psychological impact and overtreatment, must be taken into account as well. In our opinion, one of the advantages of early diagnosis should be that the patients' quality of life improves, because the stage at diagnosis and, as a result, the number of patients suffering from bone metastasis decrease, and unknown benign pathologies can be cured. These observations are not at all negligible. Our study aims to demonstrate that by using PSA as an initial test, the screening costs are reasonable and the disease incidence is just as expected.