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PURPOSE: This study proposes an automated prostate cancer (PC) lesion characterization method based on the deep neural network to determine tumor burden on 68Ga-PSMA-11 PET/CT to potentially facilitate the optimization of PSMA-directed radionuclide therapy. METHODS: We collected 68Ga-PSMA-11 PET/CT images from 193 patients with metastatic PC at three medical centers. For proof-of-concept, we focused on the detection of pelvis bone and lymph node lesions. A deep neural network (triple-combining 2.5D U-Net) was developed for the automated characterization of these lesions. The proposed method simultaneously extracts features from axial, coronal, and sagittal planes, which mimics the workflow of physicians and reduces computational and memory requirements. RESULTS: Among all the labeled lesions, the network achieved 99% precision, 99% recall, and an F1 score of 99% on bone lesion detection and 94%, precision 89% recall, and an F1 score of 92% on lymph node lesion detection. The segmentation accuracy is lower than the detection. The performance of the network was correlated with the amount of training data. CONCLUSION: We developed a deep neural network to characterize automatically the PC lesions on 68Ga-PSMA-11 PET/CT. The preliminary test within the pelvic area confirms the potential of deep learning methods. Increasing the amount of training data should further enhance the performance of the proposed method and may ultimately allow whole-body assessments.
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Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Ácido Edético/análogos & derivados , Isótopos de Gálio , Radioisótopos de Gálio , Humanos , Masculino , Redes Neurais de Computação , Oligopeptídeos , Neoplasias da Próstata/diagnóstico por imagemRESUMO
PURPOSE: 68Ga-PSMA-11 PET/CT is commonly performed at 1 h post injection (p.i.). However, various publications have demonstrated that most prostate cancer (PC) lesions exhibit higher contrast at later imaging. The aim of this study was to compare the "common" protocol of 68Ga-PSMA-11 PET/CT with a modified protocol. METHODS: In 2017, we used the following scanning protocol for 68Ga-PSMA-11 PET/CT in patients with recurrent PC: acquisition at 1 h p.i. without further preparations. From 2018, all scans were conducted at 1.5 h p.i. In addition, patients were orally hydrated with 1 L of water 0.5 h p.i. and were injected with 20 mg of furosemide 1 h p.i. Both protocols including 112 patients (2017) and 156 (modified protocol in 2018) were retrospectively compared. Rates of pathologic scans, maximum standardized uptake values (SUVmax), and tumor contrast (ratio lesion-SUVmax/background-SUVmean) as well as average standardized uptake values (SUVmean) of urinary bladder were analyzed. RESULTS: Both tumor contrast and tracer uptake were significantly (p < 0.001) higher in the novel protocol. Although statistically not significant, the rates of pathologic scans were also higher in the modified protocol: 76.3% vs. 68.8% for all PSA values including 38.9% vs. 25.0% for PSA < 0.5 ng/ml and 60.0% vs. 56.7% for PSA > 0.5-≤ 2.0 ng/ml. Average SUVmean of the urinary bladder was significantly (p < 0.001) lower with the modified protocol. CONCLUSIONS: The modified protocol, which includes a combination of delayed image acquisition at 1.5 h p.i., hydration, and furosemide resulted in higher tumor contrast and seems to have the potential to increase the rates of pathological scans, especially at low PSA levels.
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Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Ácido Edético/análogos & derivados , Isótopos de Gálio , Radioisótopos de Gálio , Humanos , Masculino , Recidiva Local de Neoplasia , Oligopeptídeos , Neoplasias da Próstata/diagnóstico por imagem , Estudos RetrospectivosRESUMO
PURPOSE: So far, there have been very few studies which provide a direct comparison between MRI and PSMA-ligand PET/CT for the detection of recurrent prostate cancer (rPC). This present study therefore aims to provide further clinical data in order to resolve this urgent clinical question, and thereby strengthen clinical recommendations. METHODS: A retrospective analysis was performed for patients who were scanned at our institution with whole-body PSMA-PET/CT (tracer: 68Ga-PSMA-11) between January 2017 and September 2018 in order to detect rPC. Amongst them, 43 underwent an additional pelvic MRI within 2 months. Both modalities were compared as follows: a consensus read of the PET data was performed by two nuclear physicians. All lesions were recorded with respect to their type and localization. The same process was conducted by two radiologists for pelvic MRI. Thereafter, both modalities were directly compared for every patient and lesion. RESULTS: Overall, 30/43 patients (69.8%) presented with a pathologic MRI and 38/43 (88.4%) with a pathologic PSMA-PET/CT of the pelvis. MRI detected 53 pelvic rPC lesions (13 of them classified as "uncertain") and PSMA-PET/CT detected 75 pelvic lesions (three classified as "uncertain"). The superiority of PSMA-PET/CT was statistically significant only if uncertain lesions were classified as false-positive. CONCLUSIONS: PSMA-PET/CT detected more pelvic lesions characteristic for rPC when compared to MRI. In order to detect rPC, a potential future scenario could be conducting first a PSMA-PET/CT. Combining the advantages of both modalities in hybrid PET/MRI scanners would be an ideal future scenario.
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Antígenos de Superfície/química , Glutamato Carboxipeptidase II/química , Imageamento por Ressonância Magnética Multiparamétrica , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Humanos , Ligantes , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Recidiva Local de Neoplasia/patologia , Neoplasias da Próstata/patologia , Valores de Referência , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
Background: Venous malformation (VM) is the most frequent type of congenital vascular malformation. In terms of functional outcome local sclerotherapy remains the most important therapeutic tool. For planning and correct estimation and prevention of complications, an exact anatomical classification of the VM is crucial. Not only the drainage, as assessed in the established classification, but also the phlebographic aspect of the internal VM structure itself plays a decisive role. In order to integrate this aspect, we aim to validate a proposal for a revised phlebographic VM classification distinguishing non-lacunar (a) and lacunar (b) types. Methods: We retrospectively analyzed all patients with VM in whom a direct puncture phlebography was performed in our clinic between 2009 and 2018 to assess morphology and flow characteristics. Phlebographic assessment included: (I) differentiation of non-lacunar vs. lacunar type; (II) drainage assignment according to the existing classification; (III) adjusted classification combining both. Inter-reader agreement was measured in percentage as well as by the Cohen's kappa coefficient (κ). Results: Overall 26 patients were classified as non-lacunar (a) and 41 patients as lacunar (b) VM. For this categorization, inter-reader agreement was 96% (κ=0.91). Classical Puig classification into types I, II, III and IV showed 87% inter-reader agreement (κ=0.78). For the adjusted classification adding the non-lacunar or lacunar characteristic to type I-IV an agreement of 82% (κ=0.77) was achieved. Conclusions: Phlebographic differentiation into non-lacunar and lacunar VM is feasible and reliable to distinguish phenotypic subgroups of patients with VM. We therefore propose to integrate this parameter of the internal VM structure into the existing classification.
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OBJECTIVE: In recent years, genotypic characterization of congenital vascular malformations (CVMs) has gained attention; however, the spectrum of clinical phenotype remains difficult to attribute to a genetic cause and is rarely described in the adult population. The aim of this study is to describe a consecutive series of adolescent and adult patients in a tertiary center, where a multimodal phenotypic approach was used for diagnosis. METHODS: We analyzed clinical findings, imaging, and laboratory results at initial presentation, and set a diagnosis according to the International Society for the Study of Vascular Anomalies (ISSVA) classification for all consecutively registered patients older than 14 years of age who were referred to the Center for Vascular Malformations at the University Hospital of Bern between 2008 and 2021. RESULTS: A total of 457 patients were included for analysis (mean age, 35 years; females, 56%). Simple CVMs were the most common (n = 361; 79%), followed by CVMs associated with other anomalies (n = 70; 15%), and combined CVMs (n = 26; 6%). Venous malformations (n = 238) were the most common CVMs overall (52%), and the most common simple CVMs (66%). Pain was the most frequently reported symptom in all patients (simple, combined, and vascular malformation with other anomalies). Pain intensity was more pronounced in simple venous and arteriovenous malformations. Clinical problems were related to the type of CVM diagnosed, with bleeding and skin ulceration in arteriovenous malformations, localized intravascular coagulopathy in venous malformations, and infectious complications in lymphatic malformations. Limb length difference occurred more often in patients with CVMs associated with other anomalies as compared with simple or combined CVM (22.9 vs 2.3%; P < .001). Soft tissue overgrowth was seen in one-quarter of all patients independent of the ISSVA group. CONCLUSIONS: In our adult and adolescent population with peripheral vascular malformations, simple venous malformations predominated, with pain as the most common clinical symptom. In one-quarter of cases, patients with vascular malformations presented with associated anomalies on tissue growth. The differentiation of clinical presentation with or without accompanying growth abnormalities need to be added to the ISSVA classification. Phenotypic characterization considering vascular and non-vascular features remains the cornerstone of diagnosis in adult as well as pediatric patients.
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Malformações Arteriovenosas , Malformações Vasculares , Feminino , Humanos , Malformações Vasculares/complicações , Malformações Vasculares/diagnóstico por imagem , Malformações Arteriovenosas/diagnóstico por imagem , Malformações Arteriovenosas/genética , Malformações Arteriovenosas/terapia , Veias/anormalidades , Dor , FenótipoRESUMO
The aim of this study was to investigate the diagnostic accuracy and reader confidence for late-gadolinium enhancement (LGE) detection of a novel free-breathing, image-based navigated 3D whole-heart LGE sequence with fat-water separation, compared to a free-breathing motion-corrected 2D LGE sequence in patients with ischemic and non-ischemic cardiomyopathy. Cardiac MRI patients including the respective sequences were retrospectively included. Two independent, blinded readers rated image quality, depiction of segmental LGE and documented acquisition time, SNR, CNR and amount of LGE. Results were compared using the Friedman or the Kruskal-Wallis test. For LGE rating, a jackknife free-response receiver operating characteristic analysis was performed with a figure of merit (FOM) calculation. Forty-two patients were included, thirty-two were examined with a 1.5 T-scanner and ten patients with a 3 T-scanner. The mean acquisition time of the 2D sequence was significantly shorter compared to the 3D sequence (07:12 min vs. 09:24 min; p < 0.001). The 3D scan time was significantly shorter when performed at 3 T compared to 1.5 T (07:47 min vs. 09:50 min; p < 0.001). There were no differences regarding SNR, CNR or amount of LGE. 3D imaging had a significantly higher FOM (0.89 vs. 0.78; p < 0.001). Overall image quality ratings were similar, but 3D sequence ratings were higher for fine anatomical structures. Free-breathing motion-corrected 3D LGE with high isotropic resolution results in enhanced LGE-detection with higher confidence and better delineation of fine structures. The acquisition time for 3D imaging was longer, but may be reduced by performing on a 3 T-scanner.
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Meios de Contraste , Gadolínio , Humanos , Cicatriz , Água , Estudos Retrospectivos , Valor Preditivo dos Testes , Imageamento por Ressonância Magnética/métodos , Imageamento Tridimensional/métodos , Aumento da Imagem/métodosRESUMO
OBJECTIVE: Arteriovenous malformations of the lower extremities (AVMLE) can present as simple or complex combined or syndromic forms (eg, Parkes Weber Syndrome). We aimed to characterize the differences in clinical presentation and natural history of these potentially life- and limb-threatening congenital vascular malformations. METHODS: We conducted a retrospective analysis of a consecutive series of patients with AVMLE who presented to a tertiary referral center in Switzerland between 2008 and 2018. Clinical baseline characteristics, D-dimer level, and course were summarized and differences between simple, non-syndromic and combined or syndromic AVMLE determined. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. RESULTS: Overall, 506 patients were prospectively enrolled in the Bernese Congenital Vascular Malformation Registry, 31 (6%) with AVMLE. There were 16 women and 15 men, with a mean age of 18 years at first diagnosis (range, 1 month to 72 years). Simple AVMLE was present in 22 (71%) and combined or syndromic AVMLE with limb overgrowth in 9 patients (29%), respectively. Common symptoms and signs were pain (n = 25; 81%), swelling (n = 21; 68%), and soft tissue hypertrophy (n = 13; 42%). Among combined or syndromic patients, three patients died from wound infection with sepsis or disseminated intravascular coagulation with bleeding complications (intracranial hemorrhage and bleeding from extensive leg ulcers). Combined or syndromic patients presented more often with bleeding (67% vs 5%; P < .001), malformation-related infection (44% vs 5%; P = .017) and leg length difference (56% vs 14%; P = .049). D-dimer levels were elevated (mean, 17,256 µg/L; range, 1557-80,000 µg/L) and angiographic appearance showed complex, mixed type of AVMs, including interstitial type IV, in all patients with combined or syndromic AVMLE. CONCLUSIONS: Patients with congenital simple AVMLE most often present with benign clinical features and rarely with complications related to hemodynamic changes. Patients with combined or syndromic AVMLE often face serious outcomes dominated by complications other than direct high-flow-related heart failure.
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Malformações Arteriovenosas Intracranianas , Adolescente , Feminino , Seguimentos , Humanos , Malformações Arteriovenosas Intracranianas/complicações , Hemorragias Intracranianas , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
ABSTRACT: A 70-year-old man presented with unspecific abdominal symptoms and weight loss was referred for a sonographic examination. Sonography revealed 3 cystic hepatic masses in an otherwise unremarkable liver. Contrast-enhanced MRI of the liver was performed to characterize the hepatic lesions and elucidate their etiology. The differential diagnosis was primarily parasitic disease or metastases with cystic transformations. 68Ga-DOTATOC PET/CT revealed the neuroendocrine origin of these lesions, confirmed by biopsy. However, the primary site of the neuroendocrine tumor remained unclear, leaving primary hepatic neuroendocrine tumor and neuroendocrine cancer of unknown primary as possible diagnostic options.
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Neoplasias Intestinais , Tumores Neuroendócrinos , Compostos Organometálicos , Neoplasias Pancreáticas , Neoplasias Gástricas , Idoso , Humanos , Masculino , Tumores Neuroendócrinos/diagnóstico por imagem , Octreotida , Tomografia por Emissão de Pósitrons combinada à Tomografia ComputadorizadaRESUMO
During angiogenesis, single endothelial cells (EC) specialize into tip cells that guide vessel sprouting towards growth factor gradients and instruct the adjacent vessel stalk. The balance between tip and stalk cells is regulated by endothelial Notch signalling through the expression of Notch ligand Delta-like 4 (Dll4) in tip cells, which suppresses a tip cell fate in adjacent stalk cells. Here we show, using genetic reporter and conditional deletion strategies, that myeloid cells regulate tip cell numbers and Dll4 expression via the Notch ligand Dll1 during vascular development in the retina. Dll1 is selectively expressed by a subpopulation of retinal myeloid cells, which progressively localizes to the sprouting vascular network. Conditional, myeloid-specific deletion of Dll1 impairs endothelial Dll4 tip-stalk gradient resulting in an increase of endothelial tip cells and EC filopodia, accompanied by an increase in vascular density and branching. In vitro, co-culture of human EC with monocyte-derived macrophages induced Dll1 upregulation in macrophages and Dll4 upregulation and an endothelial tip cell signature in EC. Furthermore, culturing human EC on recombinant DLL1 induced endothelial Dll4 expression and a tip cell program, indicating that changes are Dll1-dependent. Thus, myeloid cells regulate tip cell fate and angiogenesis through expression of Notch ligand Dll1.
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Proteínas de Ligação ao Cálcio/metabolismo , Células Mieloides/metabolismo , Receptores Notch/metabolismo , Retina/citologia , Retina/metabolismo , Vasos Retinianos/metabolismo , Animais , Biomarcadores , Proteínas de Ligação ao Cálcio/genética , Contagem de Células , Células Endoteliais/metabolismo , Imunofluorescência , Expressão Gênica , Camundongos , Camundongos Transgênicos , Neovascularização Fisiológica/genéticaRESUMO
The emerging PSMA-targeted radionuclide therapy provides an effective method for the treatment of advanced metastatic prostate cancer. To optimize the therapeutic effect and maximize the theranostic benefit, there is a need to identify and quantify target lesions prior to treatment. However, this is extremely challenging considering that a high number of lesions of heterogeneous size and uptake may distribute in a variety of anatomical context with different backgrounds. This study proposes an end-to-end deep neural network to characterize the prostate cancer lesions on PSMA imaging automatically. A 68Ga-PSMA-11 PET/CT image dataset including 71 patients with metastatic prostate cancer was collected from three medical centres for training and evaluating the proposed network. For proof-of-concept, we focus on the detection of bone and lymph node lesions in the pelvic area suggestive for metastases of prostate cancer. The preliminary test on pelvic area confirms the potential of deep learning methods. Increasing the amount of training data may further enhance the performance of the proposed deep learning method.
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Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Automação Laboratorial , Ácido Edético , Isótopos de Gálio , Radioisótopos de Gálio , Humanos , Masculino , Glicoproteínas de Membrana , Redes Neurais de Computação , Compostos Organometálicos , Neoplasias da PróstataRESUMO
INTRODUCTION: The bone scan index (BSI) was introduced as a quantitative tool for tumor involvement in bone of patients with metastatic prostate cancer (mPCa). The computer-aided diagnosis device for BSI analysis EXINIboneBSI seems to represent technical progress for the quantitative assessment of bone involvement. But it is not yet clear if the automated BSI (aBSI) could contribute to improved evaluation of progression in patients under antiandrogens or chemotherapy in contrast to the visual interpretation and/or conventional biomarkers such as the prostate-specific antigen (PSA). METHODS: In 49 mPCa patients, bone scans were performed initially and during different therapy courses. Scans were evaluated visually and by the artificial-neural-network-based expert system EXINIboneBSI. Progression of metastatic bone involvement was defined according to the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria in the visual interpretation. The computer-assisted interpretation was based on different cutoff values in relative changes of the aBSI. Additionally, assessments according to bone scanning were compared to changes in the PSA value as a potential surrogate for treatment response. RESULTS: Using a sensitive cutoff value (5% or 10%) for the relative aBSI increase led to significantly increased progression determination compared to the visual interpretation of bone scans (49% and 43% vs. 27%, p < 0.001). In 63% of the cases PSA and BSI changes matched, whereas in 18% progression was only indicated by the aBSI. A relative cutoff of 5% for the aBSI decrease could reclassify 47 serial scan pairs which were visually interpreted as stable into 22 progressive and 25 remissive scans. CONCLUSION: Distinct thresholds of the relative aBSI could help to better assess disease progression in mPCa patients. Manual corrections of the BSI values are not required in most cases. The aBSI could serve as a useful additional parameter for therapy monitoring in mPCa patients in the future.