Fit of biokinetic data in molecular radiotherapy: a machine learning approach.

BACKGROUND: In literature are reported different analytical methods (AM) to choose the proper fit model and to fit data of the time-activity curve (TAC). On the other hand, Machine Learning algorithms (ML) are increasingly used for both classification and regression tasks. The aim of this work was to investigate the possibility of employing ML both to classify the most appropriate fit model and to predict the area under the curve (τ). METHODS: Two different ML systems have been developed for classifying the fit model and to predict the biokinetic parameters. The two systems were trained and tested with synthetic TACs simulating a whole-body Fraction Injected Activity for patients affected by metastatic Differentiated Thyroid Carcinoma, administered with [131I]I-NaI. Test performances, defined as classification accuracy (CA) and percentage difference between the actual and the estimated area under the curve (Δτ), were compared with those obtained using AM varying the number of points (N) of the TACs. A comparison between AM and ML were performed using data of 20 real patients. RESULTS: As N varies, CA remains constant for ML (about 98%), while it improves for F-test (from 62 to 92%) and AICc (from 50 to 92%), as N increases. With AM, [Formula: see text] can reach down to - 67%, while using ML [Formula: see text] ranges within ± 25%. Using real TACs, there is a good agreement between τ obtained with ML system and AM. CONCLUSIONS: The employing of ML systems may be feasible, having both a better classification and a better estimation of biokinetic parameters.

Personalized dosimetry for a deeper understanding of metastatic response to high activity 131I-mIBG therapy in high risk relapsed refractory neuroblastoma.

BACKGROUND: Dosimetry in molecular radiotherapy for personalized treatment is assuming a central role in clinical management of aggressive/relapsed tumors. Relapsed/refractory metastatic high-risk neuroblastoma (rrmHR-NBL) has a poor prognosis and high-activity 131I-mIBG therapy could represent a promising strategy. The primary aim of this case series study was to report the absorbed doses to whole-body (DWB ), red marrow (DRM ) and lesions (DLesion ). A secondary aim was to correlate DLesion values to clinical outcome. METHODS: Fourteen patients affected by rrmHR-NBL were treated with high-activity 131I-mIBG therapy (two administrations separated by 15 days). The first administration was weight-based whereas the second one was dosimetry-based (achieving DWB equals to 4 Gy). In all patients DWB and DRM was assessed; 9/14 patients were selected for DLesion evaluation using planar dosimetric approach (13 lesions evaluated). Treatment response was classified as progressive and stable disease (PD and SD), partial and complete response (PR and CR) according to the International Neuroblastoma Response Criteria. Patients were divided into two groups: Responder (CR, PR, SD) and Non-Responder (PD), correlating treatment response to DLesion value. RESULTS: The cumulative DWB , DRM and DLesion ranged from (1.5; 4.5), (1.0; 2.6) and (44.2; 585.8) Gy. A linear correlation between DWB and DRM and a power law correlation between the absorbed dose to WB normalized for administered activity and the mass of the patient were observed. After treatment 3, 2, 4 and 5 patients showed CR, PR, SD and PD respectively, showing a correlation between DLesion and the two response group. CONCLUSIONS: Our experience demonstrated feasibility of high activity therapy of 131I-mIBG in rrmHR-NBL children as two administration intensive strategy. Dosimetric approach allowed a tailored high dose treatment maximizing the benefits of radionuclide therapy for pediatric patients while maintaining a safety profile. The assesment of DLesion contributed to have a deeper understaning of metabolic treatment effects.

Osteoid Osteoma of the Atlas in a Boy: Clinical and Imaging Features-A Case Report and Review of the Literature.

Osteoid osteoma is a benign osteoblastic tumor, quite uncommon in the spine. We report a case of an osteoid osteoma involving the atlas in a 6-year-old boy, who presented with suboccipital pain and torticollis. Initial radiological findings were ambiguous as magnetic resonance imaging showed mainly edema of upper cervical soft tissues. The subsequent computed tomography depicted a lesion of left lamina of C1. As conservative treatment failed, the lesion was surgically resected and the patient became pain free. To our knowledge, this is the first case of osteoid osteoma involving the atlas associated with abnormal soft tissue reaction reported in literature.

Liver steatosis is highly prevalent and is associated with metabolic risk factors and liver fibrosis in adult patients with type 1 Gaucher disease.

BACKGROUND AND AIMS: Gaucher disease (GD) is associated with peculiar metabolic abnormalities (ie hypermetabolic state, peripheral insulin resistance, dyslipidaemia), partially reverted by enzyme replacement therapy (ERT) at the expense of weight gain. Such metabolic alterations together with an unhealthy lifestyle acquired by an ageing GD population may favour the development of liver steatosis. We aimed at evaluating the prevalence of significant liver steatosis and at identifying the factors associated with liver steatosis in a cohort of patients with type 1 GD. METHODS: Twenty adult type 1 GD patients from an Italian academic referral centre were prospectively submitted to vibration-controlled transient elastography (Fibroscan®) with controlled attenuation parameter (CAP); significant steatosis was defined as CAP values ≥250 dB/min. RESULTS: Median CAP values were 234 [165-358] dB/min and 8 patients (40%) had significant steatosis. Significant steatosis was associated with indices of adiposity (weight, BMI and waist circumference), high blood pressure, insulin resistance and metabolic syndrome. GD-related variables and dose and duration of ERT were not associated with significant steatosis. In the subgroup of 16 patients on stable ERT for at least 24 months, CAP resulted significantly and positively associated with liver stiffness (rho 0.559, P = .024). CONCLUSIONS: Significant steatosis is highly prevalent in adult type 1 GD patients and is strongly associated with a worse metabolic profile, featuring metabolic dysfunction-associated fatty liver disease (MAFLD). MAFLD may determine liver fibrosis progression in GD patients on stable ERT and may be a risk factor for long-term liver-related complications.

Prevalence and predictors of liver fibrosis evaluated by vibration controlled transient elastography in type 1 Gaucher disease.

BACKGROUND & AIMS: Long-term liver-related complications of Gaucher disease (GD) include cirrhosis, portal hypertension and hepatocellular carcinoma. Although liver fibrosis is the main determinant of adverse liver-related clinical outcomes, it has rarely been evaluated in previously published cohorts of GD patients. We aimed at: assessing the prevalence of significant liver fibrosis in a cohort of patients with type 1 GD; identifying its predictors among GD-related variables, enzyme replacement therapy (ERT) and metabolic features. METHODS: 37 adult type 1 GD patients from two Italian academic referral centers were prospectively submitted to vibration controlled transient elastography (Fibroscan®); significant fibrosis was defined as liver stiffness ≥7 kPa. RESULTS: Median liver stiffness was 4.6 [3-15.1] kPa and 7 patients (19%) had significant fibrosis. Significant fibrosis was associated with splenectomy (p = .046) and with scores (DS3: p = .002; SSI: p = .026) and biomarkers (ACE: p = .016; HDL cholesterol: p = .004) of GD severity. Length of ERT was significantly lower in GD patients with significant fibrosis. In the subgroup of 29 patients who were on stable ERT for at least 24 months, further to splenectomy, GD severity and non-N370S GBA1 genotypes, also diastolic blood pressure, BMI and the number of metabolic syndrome (MetS) components emerged as factors significantly associated with significant fibrosis. CONCLUSIONS: Significant fibrosis is present in a remarkable proportion of adult type 1 GD patients. Splenectomy, GD severity and GBA1 genotypes are major GD-related predictors of liver fibrosis. Length of ERT is inversely correlated with liver disease in GD patients, suggesting a beneficial effect of ERT on liver fibrosis. However, GD patients on stable ERT should be monitored for metabolic complications, since MetS features may enhance liver disease progression despite optimal GD control.

Quantification of scatter radiation from radiographic procedures in a neonatal intensive care unit.

BACKGROUND: In a neonatal intensive care unit (NICU), preterm infants are often exposed to a large number of radiographic examinations, which could cause adjacent neonates, family caregivers and staff members to be exposed to a dose amount due to scatter radiation. OBJECTIVE: To provide information on scatter radiation exposure levels in a NICU, to compare these values with the effective dose limits established by the European Union and to evaluate the effectiveness of radiation protection devices in this setting. MATERIALS AND METHODS: Radiation exposure levels due to scatter radiation were estimated by passive detectors (thermoluminescent dosimeters) and direct dosimetric measurements (with a dose rate meter); in the latter case, an angular map of the scatter dose distribution was achieved. RESULTS: The dose due to scatter radiation to staff in our setting is approximately 160 µSv/year, which is markedly lower than the effective dose limit for workers established by the European Union (20 mSv/year). The doses range between 0.012 and 0.095 µSv/radiograph. Considering a mean hospitalization period of 3 months and our NICU workload, the corresponding scatter radiation dose to an adjacent patient and/or his/her caregiver is at most 40 µSv. CONCLUSION: For distances greater than 1 m from the irradiation field, both scatter dose absorbed by a staff member during a year and that by an adjacent patient and/or his/her caregiver during hospitalization is less than 1 mSv, which is the exposure limit for public members in a year.

Biopsy is not necessary for the diagnosis of soft tissue hemangiomas.

OBJECTIVE: To describe the clinical and ultrasonography (US) findings of soft tissue hemangiomas, and to compare with the results of histologic diagnosis after US-guided biopsy. METHOD AND MATERIALS: We retrospectively studied the files of 97 patients (48 female, 49 male; mean age, 34 years; range 4-84 years) with soft tissue hemangiomas diagnosed from 2004 to 2011. Mean follow-up was 9 years (range 7-13 years). Clinical presentation included intermittent mild pain associated with a soft tissue swelling/palpable mass in all patients, chronic pain and increased local heat in 29 patients, local swelling and decreased range of motion of the adjacent joint in 45 patients, and all the above symptoms in 23 patients. B-mode and color Doppler US evaluation included the site, location, size, shape, margins, presence of calcifications, echo structure and echogenicity. All patients had US-guided biopsy for histologic analysis. RESULTS: US-guided biopsy and histology confirmed the diagnosis of soft tissue hemangioma in 92 of the 97 lesions (94.8%). Histologic examination of the remaining five lesions showed nodular fasciitis (two lesions), endometriosis (one lesion), hemangioendothelioma (two lesions); US of these lesions showed variable size, irregular margins, and deep-seated location. Histologically documented soft tissue hemangiomas were most commonly superficial (74 lesions) and arteriovenous (45 lesions). Shape was most commonly oval (fusiform), margins were most commonly not well defined (irregular, hazing but circumscribed), phleboliths were more common in deep-seated lesions, echo structure was heterogeneous, and echogenicity was most commonly hyperechogen and involuting. CONCLUSION: Clinical presentation and typical B-mode and color Doppler US findings are adequate for the diagnosis of soft tissue hemangiomas without the need for biopsy and histologic analysis. If any clinical or US doubt, an US-guided biopsy should be performed.

A novel method for CT dosimetry with a suspended phantom setup.

PURPOSE: This work presents a method for estimating CT dosimetric indices with a prototype designed for suspending the phantom/ion chamber system fixed at the CT isocenter. The purpose of this study was to validate the proposed methodology, which can be used to provide a direct assessment of dosimetric indices in helical scans. METHODS: The method is based on a reference setup in which the measuring system for CT dosimetry is in a stationary configuration, i.e. not bound to the CT table, and on a mathematical formalism developed for the proposed reference system. The reliability of the method was demonstrated through a set of experimental measurements. Firstly, dosimetric indices were measured with the new method and compared with the indices obtained with the procedure currently used for CT dosimetry (measuring system bound to the CT table). Secondly, dosimetric indices measured with the new method were compared with those displayed on the CT console. RESULTS: There is good agreement between the dosimetric indices obtained with the standard setup and those obtained with the suspended phantom setup, within the expected range of errors. The difference between dosimetric indices estimated with the proposed method and those displayed on the CT console is below 2%. CONCLUSIONS: The method enables CT dosimetry to be performed with the dose detector in a stationary longitudinal position thanks to the newly introduced suspended phantom setup. Using this approach, CT dose can be assessed for high pitch helical scans, acquisitions without complete tube rotation and for cases where dynamic collimation is used.

Mechanically Assisted Total Cavopulmonary Connection With an Axial Flow Pump: Computational and In Vivo Study.

A relevant number of patients undergoing total cavopulmonary connection (TCPC) experience heart failure (HF). Heart transplant is then the final option when all other treatments fail. The axial flow blood pumps are now the state of the art; however, there is little experience in low-pressure circuits, such as support of the right ventricle or even a TCPC circulation. A new T-shaped model of mechanically assisted TCPC using the "Jarvik Child 2000" axial pump, (flow rates between 1 and 3 L/m in a range of 5000-9000 rpm) was designed, simulated numerically, and then tested in animals. Eight sheep (42-45 kg) were studied: two pilot studies, four pump-supported (PS) TCPC for 3 h, and two not pump-supported (NPS) TCPC. In the PS, the axial pump was set to maintain the baseline cardiac output (CO). Pressures, CO, systemic and pulmonary vascular resistance, lactate levels, and blood gases were recorded for 3 h. Computational fluid dynamics (CFD) study allows us to set the feasible operating condition and the safety margins to minimize the venous collapse risk. In the NPS animals, a circulatory deterioration, with increasing lactate level, occurred rapidly. In the PS animals, there was a stable cardiac index of 2.7 ± 1.4 L/min/m(2), central venous pressure of 12.3 ± 1 mm Hg, and a mean pulmonary artery pressure (PAP) of 18.1 ± 6 after 3 h of support up to 9000 rpm. systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), blood gasses, and arterial lactate levels remained stable to baseline values. No caval collapse occurred. A new pediatric axial flow pump provides normal CO and physiologic stability in a new T-shaped model of TCPC in sheep, in vivo. CFD and in vivo data showed that this experimental arrangement will allow us to evaluate the potential for mechanical support in patients with Fontan failure avoiding major adverse events.