Application Of Positron Emission Tomography Research Articles

Application of Positron Emission Tomography in the Detection of Myocardial Metabolism in Pig Ventricular Fibrillation and Asphyxiation Cardiac Arrest Models after Resuscitation

ObjectiveTo study the application of positron emission tomography (PET) in detection of myocardial metabolism in pig ventricular fibrillation and asphyxiation cardiac arrest models after resuscitation. MethodsThirty-two healthy miniature pigs were randomized into a ventricular fibrillation cardiac arrest (VFCA) group (n=16) and an asphyxiation cardiac arrest (ACA) group (n=16). Cardiac arrest (CA) was induced by programmed electric stimulation or endotracheal tube clamping followed by cardiopulmonary resuscitation (CPR) and defibrillation. At four hours and 24 h after spontaneous circulation was achieved, myocardial metabolism was assessed by PET. 18F-FDG myocardial uptake in PET was analyzed and the maximum standardized uptake value (SUVmax) was measured. ResultsSpontaneous circulation was 100% and 62.5% in VFCA group and ACA group, respectively. PET demonstrated that the myocardial metabolism injuries was more severe and widespread after ACA than after VFCA. The SUVmax was higher in VFCA group than in ACA group (P<0.01). In VFCA group, SUVmax at 24 h after spontaneous circulation increased to the level of baseline. ConclusionACA causes more severe cardiac metabolism injuries than VFCA. Myocardial dysfunction is associated with less successful resuscitation. Myocardial stunning does occur with VFCA but not with ACA.

In vivo PET imaging of beta-amyloid deposition in mouse models of Alzheimer's disease with a high specific activity PET imaging agent [(18)F]flutemetamol.

BackgroundThe purpose of the study was to evaluate the applicability of 18F-labelled amyloid imaging positron emission tomography (PET) agent [18F]flutemetamol to detect changes in brain beta-amyloid (Aβ) deposition in vivo in APP23, Tg2576 and APPswe-PS1dE9 mouse models of Alzheimer's disease. We expected that the high specific activity of [18F]flutemetamol would make it an attractive small animal Aβ imaging agent.Methods[18F]flutemetamol uptake in the mouse brain was evaluated in vivo at 9 to 22 months of age with an Inveon Multimodality PET/CT camera (Siemens Medical Solutions USA, Knoxville, TN, USA). Retention in the frontal cortex (FC) was evaluated by Logan distribution volume ratios (DVR) and FC/cerebellum (CB) ratios during the late washout phase (50 to 60 min). [18F]flutemetamol binding to Aβ was also evaluated in brain slices by in vitro and ex vivo autoradiography. The amount of Aβ in the brain slices was determined with Thioflavin S and anti-Aβ1−40 immunohistochemistry.ResultsIn APP23 mice, [18F]flutemetamol retention in the FC increased from 9 to 18 months. In younger mice, DVR and FC/CB50-60 were 0.88 (0.81) and 0.88 (0.89) at 9 months (N = 2), and 0.98 (0.93) at 12 months (N = 1), respectively. In older mice, DVR and FC/CB50-60 were 1.16 (1.15) at 15 months (N = 1), 1.13 (1.16) and 1.35 (1.35) at 18 months (N = 2), and 1.05 (1.31) at 21 months (N = 1). In Tg2576 mice, DVR and FC/CB50-60 showed modest increasing trends but also high variability. In APPswe-PS1dE9 mice, DVR and FC/CB50-60 did not increase with age. Thioflavin S and anti-Aβ1−40 positive Aβ deposits were present in all transgenic mice at 19 to 22 months, and they co-localized with [18F]flutemetamol binding in the brain slices examined with in vitro and ex vivo autoradiography.ConclusionsIncreased [18F]flutemetamol retention in the brain was detected in old APP23 mice in vivo. However, the high specific activity of [18F]flutemetamol did not provide a notable advantage in Tg2576 and APPswe-PS1dE9 mice compared to the previously evaluated structural analogue [11C]PIB. For its practical benefits, [18F]flutemetamol imaging with a suitable mouse model like APP23 is an attractive alternative.

Application of partial volume effect correction and 4D PET in the quantification of FDG avid lung lesions.

The aim of this study is to assess a software-based method with semiautomated correction for partial volume effect (PVE) to quantify the metabolic activity of pulmonary malignancies in patients who underwent non-gated and respiratory-gated 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG)-positron emission tomography (PET)/x-ray computed tomography(CT). The study included 106 lesions of 55 lung cancer patients who underwent respiratory-gated FDG-PET/CT for radiation therapy treatment planning. Volumetric PET/CT parameters were determined by using 4D PET/CT and non-gated PET/CT images. We used a semiautomated program employing an adaptive contrast-oriented thresholding algorithm for lesion delineation as well as a lesion-based partial volume effect correction algorithm. We compared respiratory-gated parameters with non-gated parameters by using pairwise comparison and interclass correlation coefficient assessment. In a multivariable regression analysis, we also examined factors, which can affect quantification accuracy, including the size of lesion and the location of tumor. This study showed that quantification of volumetric parameters of 4D PET/CT images using an adaptive contrast-oriented thresholding algorithm and 3D lesion-based partial volume correction is feasible. We observed slight increase in FDG uptake by using PET/CT volumetric parameters in comparison of highest respiratory-gated values with non-gated values. After correction for partial volume effect, the mean standardized uptake value (SUVmean) and total lesion glycolysis (TLG) increased substantially (p value <0.001). However, we did not observe a clinically significant difference between partial volume corrected parameters of respiratory-gated and non-gated PET/CT scans. Regression analysis showed that tumor volume was the main predictor of quantification inaccuracy caused by partial volume effect. Based on this study, assessment of volumetric PET/CT parameters and partial volume effect correction for accurate quantification of lung malignant lesions by using respiratory non-gated PET images are feasible and it is comparable to gated measurements. Partial volume correction increased both the respiratory-gated and non-gated values significantly and appears to be the dominant source of quantification error of lung lesions.

FDG PET for gauging of sarcoid disease activity.

Fluorodeoxyglucose (FDG), labeled with a positron emitting fluorine-18 ((18)F), is a synthesized glucose analogue and is well known for its application in a wide variety of clinical conditions such as cancer. Visualizing metabolic activity of inflammation is another application of FDG in positron emission tomography (PET). Here, active granulomas appear to have a high affinity for FDG, which is reflected in a high sensitivity of FDG PET imaging. This has led to novel applications of FDG PET in sarcoidosis diagnosis and management. Although chest radiography and high-resolution computed tomography are still the cornerstones of diagnosing pulmonary involvement, FDG PET appears to be superior to both techniques in imaging active sites of disease. FDG PET also correlates well with serum biomarkers such as soluble interleukin-2 receptor in symptomatic patients, and even visualizes active lesions in the context of normal serum biomarkers. Moreover, FDG PET activity in lung parenchyma correlates with decrease of lung function values over time. Also in cardiac involvement in sarcoidosis, FDG PET is a promising technique complementary to magnetic resonance imaging, especially in guiding treatment. New developments, such as applications for quantitative organ-specific measurement, are proceeding and will probably enhance the clinical implementation of FDG PET in sarcoidosis.

Current trends in using PET radiopharmaceuticals for diagnostics in oncology

Nuclear medicine is an important field of modern medicine, particularly thanks to its role in in vivo imaging of important processes in human organism. This is possible thanks to the use of radiopharmaceuticals, specific substances labeled by radioactive nuclide, its distribution in the body can be visualized by specialized scanners and, based on the knowledge of physiological patterns, dia-gnosis can be determined. Positron emission tomography (PET) is a modern and in many ways indispensable method of nuclear medicine. The spectrum of radiopharmaceuticals available in recent years is broadening thanks to a coordinated effort of manufacturers of synthesis equipment, chemists and potential users - physicians. This review focuses on the development in the PET radiopharmaceutical field in the last five years, with an emphasis on oncological applications of PET.

Effects of reflector and crystal surface on the performance of a depth-encoding PET detector with dual-ended readout.

Depth encoding detectors are required to improve the spatial resolution and spatial resolution uniformity of small animal positron emission tomography (PET) scanners, as well as dedicated breast and brain scanners. Depth of interaction (DOI) can be measured by using dual-ended readout of lutetium oxyorthosilicate (LSO) scintillator arrays with position-sensitive avalanche photodiodes. Inter-crystal reflectors and crystal surface treatments play important roles in determining the performance of dual-ended detectors. In this paper, the authors evaluated five LSO arrays made with three different intercrystal reflectors and with either polished or unpolished crystal surfaces. The crystal size in all arrays was 1.5 mm, which is typical of the detector size used in small animal and dedicated breast scanners. The LSO arrays were measured with dual-ended readout and were compared in terms of flood histogram, energy resolution, and DOI resolution performance. The four arrays using enhanced specular reflector (ESR) and Toray reflector provided similar quality flood histograms and the array using Crystal Wrap reflector gave the worst flood histogram. The two arrays using ESR reflector provided the best energy resolution and the array using Crystal Wrap reflector yielded the worst energy resolution. All arrays except the polished ESR array provided good DOI resolution ranging from 1.9 mm to 2.9 mm. DOI resolution improved as the gradient in light collection efficiency with depth (GLCED) increased. The geometric mean energies were also calculated for these dual-ended readout detectors as an alternative to the conventional summed total energy. It was shown that the geometric mean energy is advantageous in that it provides more uniform photopeak amplitude at different depths for arrays with high GLCED, and is beneficial in event selection by allowing a fixed energy window independent of depth. A new method of DOI calculation that improved the linearity of DOI ratio vs depth and simplifies the DOI calibration procedure also was developed and tested. The results of these studies provide useful guidance in selecting the proper reflectors and crystal surface treatments when LSO arrays are used for high-resolution PET applications in small animal scanners or dedicated breast and brain scanners.

On the Quantification Accuracy, Homogeneity, and Stability of Simultaneous Positron Emission Tomography/Magnetic Resonance Imaging Systems

A potential major application of simultaneous avalanche photodiode-based positron emission tomography (PET)/magnetic resonance imaging (MRI) systems are quantitative brain studies for cerebral blood flow measurements in combination with blood-oxygen-level-dependent or perfusion MRI, requiring a high performance for both modalities. Thus, we evaluated PET quantification accuracy and homogeneity for 2 different simultaneous PET/MRI systems (whole-body and brain scanner) compared with those of a state-of-the-art PET detector (PET/computed tomography) using phantom studies. In addition, we investigated the long-term stability of PET and quality of functional MRI measurements of a clinical whole-body PET/MRI scanner. Phantom measurements were conducted using spheres filled with [F]-fluoride distributed in a homogeneous cylinder phantom at different positions inside the PET field of view. Recovery values and standard deviations were extracted from resulting PET images. The influence of magnetic resonance-based attenuation correction and that of activity outside the PET field of view on the recovery values of these spheres was evaluated. Furthermore, long-term PET stability of the whole-body PET/MRI system was assessed by evaluating position profiles, energy spectra, count rates, and recovery values from [Ge]-phantom scans. Functional MRI applicability was tested in accordance with the functional Biomedical Information Research Network procedure. The BrainPET system showed high recovery values (up to 99%) but also increased variability (up to 7.4%). Significant underestimations in PET quantification near activity outside the PET field of view were found (up to 80%). Using magnetic resonance-based attenuation correction led to an underestimation in PET activity of approximately 7%. In distinction, the whole-body PET/MRI system revealed performance similar to the PET/computed tomographic scanner (recovery values up to approximately 60% with a variability of approximately 4%). Long-term stability and fMRI performance of the whole-body PET/MRI scanner showed no degradation compared with stand-alone systems. Homogeneity and accuracy of avalanche photodiode-based PET detectors is comparable with those of the state-of-the-art detectors based on photomultiplier tubes. However, attenuation correction on PET/MRI systems has to be adapted carefully for quantitative PET measurements. The BrainPET system needs improved scatter correction to perform quantitative brain studies. The whole-body PET/MRI scanner, however, is applicable for quantitative brain studies.

The Role of PET Imaging Before, During, and After Percutaneous Hepatic and Pulmonary Tumor Ablation.

The combination of anatomic and metabolic information provided by positron emission tomography (PET)/computed tomography makes it an important imaging modality to be obtained in conjunction with percutaneous ablation of primary and secondary malignancies of the lungs and liver. Advantages include more accurate preprocedural staging to determine appropriate treatment options, intraprocedural guidance to target difficult-to-see lesions, and postprocedural detection of residual or recurrent disease. Future applications of PET include strategies for intraprocedural guidance with real-time determination of incompletely ablated tumor, and combined PET/magnetic resonance imaging before, during, and after ablation for greater sensitivity to detect disease.

Positron emission tomography/computerized tomography in lung cancer.

Positron emission tomography (PET) using 2-(18F)-flouro-2-deoxy-D-glucose (FDG) has emerged as a useful tool in the clinical work-up of lung cancer. This review article provides an overview of applications of PET in diagnosis, staging, treatment response evaluation, radiotherapy planning, recurrence assessment and prognostication of lung cancer.

Characterization of a module with pixelated CdTe detectors for possible PET, PEM and compton camera applications

We present the measurement of the energy resolution and the impact of charge sharing for a pixel CdTe detector. This detector will be used in a novel conceptual design for diagnostic systems in the field of nuclear medicine such as positron emission tomography (PET), positron emission mammography (PEM) and Compton camera. The detector dimensions are 10 mm × 10 mm × 2 mm and with a pixel pitch of 1 mm × 1 mm. The pixel CdTe detector is a Schottky diode and it was tested at a bias of -1000 V. The VATAGP7.1 frontend ASIC was used for the readout of the pixel detector and the corresponding single channel electronic noise was found to be σ < 2 keV for all the pixels. We have achieved an energy resolution, FWHM/Epeak, of 7.1%, 4.5% and 0.98% for 59.5, 122 and 511 keV respectively.The study of the charge sharing shows that 16% of the events deposit part of their energy in the adjacent pixel.

Phosphinic Acid Functionalized Polyazacycloalkane Chelators for Radiodiagnostics and Radiotherapeutics: Unique Characteristics and Applications

Given the wide application of positron emission tomography (PET), positron-emitting metal radionuclides have received much attention recently. Of these, gallium-68 has become particularly popular, as it is the only PET nuclide commercially available from radionuclide generators, therefore allowing local production of PET radiotracers independent of an on-site cyclotron. Hence, interest in optimized bifunctional chelators for the elaboration of (68) Ga-labeled bioconjugates has been rekindled as well, resulting in the development of improved triazacyclononane-triphosphinate (TRAP) ligand structures. The most remarkable features of these ligands are unparalleled selectivity for Ga(III) , rapid Ga(III) complexation kinetics, extraordinarily high thermodynamic stability, and kinetic inertness of the respective Ga(III) chelates. As a result, TRAP chelators exhibit very favorable (68) Ga-labeling properties. Based on the scaffolds NOPO (1,4,7-triazacyclononane-1,4-bis[methylene(hydroxymethyl)phosphinic acid]-7-[methylene(2-carboxyethyl)phosphinic acid]) and TRAP-Pr, tailored for convenient preparation of (68) Ga-labeled monomeric and multimeric bioconjugates, a variety of novel (68) Ga radiopharmaceuticals have been synthesized. These include bisphosphonates, somatostatin receptor ligands, prostate-specific membrane antigen (PSMA)-targeting peptides, and cyclic RGD pentapeptides, for in vivo PET imaging of bone, neuroendocrine tumors, prostate cancer, and integrin expression, respectively. Furthermore, TRAP-based (68) Ga-labeled gadolinium(III) complexes have been proposed as bimodal probes for PET/MRI, and a cyclen-based analogue of TRAP-Pr has been suggested for the elaboration of targeted radiotherapeutics comprising radiolanthanide ions. Thus, polyazacycloalkane-based polyphosphinic acid chelators are a powerful toolbox for pharmaceutical research, particularly for the development of (68) Ga radiopharmaceuticals.

Performance of FBK high-density SiPM technology coupled to Ce:LYSO and Ce:GAGG for TOF-PET

This paper presents the performance, in terms of energy and timing resolution, of high-density silicon photomultipliers (SiPMs) produced at Fondazione Bruno Kessler for time-of-flight positron emission tomography application. The new SiPM technology allows us to produce devices with a small cell size maintaining a high fill factor (FF). The sensors considered in this paper are composed by 30 × 30 μm2 cells with a FF exceeding 70% to cover a total area of 4 × 4 mm2. The SiPM performance was evaluated using two types of scintillators (Ce:LYSO and Ce:GaGG) both with a short height (5 mm) in order to minimize the time jitter caused by light propagation in the crystal. With Ce:LYSO, an energy resolution of 9.0% FWHM at 511 keV and a coincidence resolving time (CRT) of 125 ps FWHM were obtained at −20 °C. With Ce:GaGG, an energy resolution of 6.4% FWHM and a CRT of 260 ps FWHM were achieved at the same temperature. The novel SiPM technology, combining a high PDE with a low correlated noise (i.e., crosstalk and afterpulse), allows us to improve the state-of-the-art of energy and timing resolution with both the tested crystals.

Machine Learning Optimisation for Realistic 2D and 3D PET-CT Phantom Study

An experimental study using artificial neural network (ANN) is carried out to achieve the optimal network architecture for proposed positron emission tomography (PET) application. 55 experimental phantom datasets acquired under clinically realistic conditions with different 2-D and 3-D acquisitions and image reconstruction parameters along with 2min, 3min and 4min scan times per bed are used in this study. The best scanner parameters are determined based on the ANN experimental evaluation of the proposed datasets. The analysis methodology of phantom PET data has shown promising results and can successfully classify and quantify malignant lesions in clinically realistic datasets.

Application of positron emission tomography and 2-[18F]fluoro-2-deoxy-d-glucose for visualization and quantification of solute transport in plant tissues

AbstractThe aim of the presented work was to evaluate the uptake and distribution of 2-fluoro-2-deoxy-d-glucose spiked with 18F (2-[18F]FDG) in tissues of tobacco plants (Nicotiana tabacum L.) by positron emission tomography and multivariate data analysis after the immersion of the petiole of excised leaf or root of a tobacco plant in a glucose solution. From individual experiments it was found that increasing glucose concentration (c glu) in the applied solution resulted in significantly higher 2-[18F]FDG diffusion and translocation within the leaf parenchyma. More than a four times increase of the 2-[18F]FDG translocation into the aboveground parts of the tobacco plant in case of the root immersion in solution with 100-times higher c glu in comparison with the control (c glu = 0.00762 mg cm−3) was determined. These facts were not confirmed only visually on basis of the obtained 3D images, but also by the increasing coincidence transfer factor (TFc) values defined by the ratio of the number of analyzed coincidences in the non-immersed parts of leaf or plant to coincidences in leaf petiole or root immersed in the solution. Cluster and principal component analysis suggest that the 2-[18F]FDG uptake by the petiole of excised leaf and root system was realized by different mechanisms; also, the 3D image quality is influenced by the initial radioactivity of the applied solution.

18F-labeling using click cycloadditions.

Due to expanding applications of positron emission tomography (PET) there is a demand for developing new techniques to introduce fluorine-18 (t 1/2 = 109.8 min). Considering that most novel PET tracers are sensitive biomolecules and that direct introduction of fluorine-18 often needs harsh conditions, the insertion of 18F in those molecules poses an exceeding challenge. Two major challenges during 18F-labeling are a regioselective introduction and a fast and high yielding way under mild conditions. Furthermore, attention has to be paid to functionalities, which are usually present in complex structures of the target molecule. The Cu-catalyzed azide-alkyne cycloaddition (CuAAC) and several copper-free click reactions represent such methods for radiolabeling of sensitive molecules under the above-mentioned criteria. This minireview will provide a quick overview about the development of novel 18F-labeled prosthetic groups for click cycloadditions and will summarize recent trends in copper-catalyzed and copper-free click 18F-cycloadditions.

Application of fluorodeoxyglucose positron emission tomography in the management of head and neck cancers.

The use of fluorodeoxyglucose positron emission tomography (FDG PET) scan technology in the management of head and neck cancers continues to increase. We discuss the biology of FDG uptake in malignant lesions and also discuss the physics of PET imaging. The various parameters described to quantify FDG uptake in cancers including standardized uptake value, metabolic tumor volume and total lesion glycolysis are presented. PET scans have found a significant role in the diagnosis and staging of head and neck cancers. They are also being increasingly used in radiation therapy treatment planning. Many groups have also used PET derived values to serve as prognostic indicators of outcomes including loco-regional control and overall survival. FDG PET scans are also proving very useful in assessing the efficacy of treatment and management and follow-up of head and neck cancer patients. This review article focuses on the role of FDG-PET computed tomography scans in these areas for squamous cell carcinoma of the head and neck. We present the current state of the art and speculate on the future applications of this technology including protocol development, newer imaging methods such as combined magnetic resonance and PET imaging and novel radiopharmaceuticals that can be used to further study tumor biology.

Positron emission tomography to assess hypoxia and perfusion in lung cancer.

In lung cancer, tumor hypoxia is a characteristic feature, which is associated with a poor prognosis and resistance to both radiation therapy and chemotherapy. As the development of tumor hypoxia is associated with decreased perfusion, perfusion measurements provide more insight into the relation between hypoxia and perfusion in malignant tumors. Positron emission tomography (PET) is a highly sensitive nuclear imaging technique that is suited for non-invasive in vivo monitoring of dynamic processes including hypoxia and its associated parameter perfusion. The PET technique enables quantitative assessment of hypoxia and perfusion in tumors. To this end, consecutive PET scans can be performed in one scan session. Using different hypoxia tracers, PET imaging may provide insight into the prognostic significance of hypoxia and perfusion in lung cancer. In addition, PET studies may play an important role in various stages of personalized medicine, as these may help to select patients for specific treatments including radiation therapy, hypoxia modifying therapies, and antiangiogenic strategies. In addition, specific PET tracers can be applied for monitoring therapy. The present review provides an overview of the clinical applications of PET to measure hypoxia and perfusion in lung cancer. Available PET tracers and their characteristics as well as the applications of combined hypoxia and perfusion PET imaging are discussed.

Application of positron emission tomography with 18ffdg in combined diagnosis of anxiety and depressive disorders in elderly patients with chronic heart failure

35 patients with chronic cardiac failure of the third functional class and anxiety depressive disorders were examined. The screening group consisted of 35 patients with chronic cardiac insufficiency without affective disorders. Evaluation of the clinical state was carried out by echocardiography, 6 minute walk and estimation of therapy compliance. Severity of the symptoms of anxiety and depressive disorders were studied by MMPI test, Beck`s test, Hamilton`s scale, Spielberg scale. PET with 18FFDG was carried out on PET tomographs «EcatExact 47» and «Ecat Exact HR+» (Siemens, Germany). It was found that anxiety depressive disorders have negative effect on the clinical state and the therapy compliance in the patients with chronic cardiac failure. Significant correlation between the clinical data and the brain 18FFDG PET results was seen in most cases.

Present Role of Positron Emission Tomography in the Diagnosis and Monitoring of Peripheral Inflammatory Arthritis: A Systematic Review

To determine the current status of positron emission tomography (PET) as a tool for diagnosis and monitoring of peripheral inflammatory arthritis (IA). For conducting this systematic review, the PubMed (Medline), Embase, and Cochrane Library databases were searched until December 31, 2012. Studies of PET for diagnosis and/or therapy monitoring of peripheral IA were included. Data were summarized qualitatively using best evidence synthesis. Eighteen articles met our inclusion criteria. The majority of studies were feasibility studies with varying methods applied. All studies demonstrated that PET visualized IA with high sensitivity, corresponding to clinical assessments. PET outcome of clinically active IA also matched that of ultrasound and magnetic resonance imaging. PET differentiates from other modalities by (quantitative) imaging of molecular sites in the synovium. The first studies reporting on the potential clinical applications of PET to image subclinical synovitis in preclinical RA and during therapy have been published. The results are promising, but the number and study populations of these studies are still limited. Thus far, a limited number of PET studies addressing IA imaging have been published. The PET modality seems to offer highly sensitive and potentially specific imaging of IA at the (quantitative) molecular level. Clinical application studies for early diagnostics and therapy monitoring are arising, but these topics should be further explored in future studies with larger cohorts. For integration in clinical practice, aspects such as radiation burden and cost-effectiveness should also be taken into account.

Multiagent imaging of the brain

Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are in vivo imaging techniques that, using a wide range of tracers, allow the non-invasive tracking of pathophysiological processes in healthy and diseased brain. One of most promising of the various PET and SPECT applications is the investigation of pathophysiological aspects of neurodegenerative disorders. This is an extremely important area of investigation given the aging of the global population and the high prevalence of brain disorders such as Alzheimer’s disease and Parkinson’s disease in elderly persons. Clinical translation of advances in molecular imaging research into clinical practice may, by overcoming the limitations of a diagnostic approach that relies exclusively on clinical judgment and structural imaging, lead to better clinical management of affected patients.