Cutaneous squamous cell carcinoma of the lip successfully treated with rhenium-188 brachytherapy.

Cutaneous squamous cell carcinoma (SCC) is the second most common form of skin cancer. In most cases, non-invasive SCC has a good prognosis and is curable by surgical resection. Nevertheless, a small percentage of patients pose specific management problems due to the technical difficulty of maintaining function and aesthetics because of the size or location of the tumor. An emerging therapeutic approach with high-dose brachytherapy using a nonsealed rhenium-188 resin, commercially known as Rhenium-Skin Cancer Therapy®, has been shown to be highly effective in non-invasive carcinoma, up to a thickness of 2-3 mm.

Applications of Artificial Intelligence and Radiomics in Molecular Hybrid Imaging and Theragnostics for Neuro-Endocrine Neoplasms (NENs).

Nuclear medicine has acquired a crucial role in the management of patients with neuroendocrine neoplasms (NENs) by improving the accuracy of diagnosis and staging as well as their risk stratification and personalized therapies, including radioligand therapies (RLT). Artificial intelligence (AI) and radiomics can enable physicians to further improve the overall efficiency and accuracy of the use of these tools in both diagnostic and therapeutic settings by improving the prediction of the tumor grade, differential diagnosis from other malignancies, assessment of tumor behavior and aggressiveness, and prediction of treatment response. This systematic review aims to describe the state-of-the-art AI and radiomics applications in the molecular imaging of NENs.

Radiomics and artificial intelligence in prostate cancer: new tools for molecular hybrid imaging and theragnostics.

In prostate cancer (PCa), the use of new radiopharmaceuticals has improved the accuracy of diagnosis and staging, refined surveillance strategies, and introduced specific and personalized radioreceptor therapies. Nuclear medicine, therefore, holds great promise for improving the quality of life of PCa patients, through managing and processing a vast amount of molecular imaging data and beyond, using a multi-omics approach and improving patients' risk-stratification for tailored medicine. Artificial intelligence (AI) and radiomics may allow clinicians to improve the overall efficiency and accuracy of using these "big data" in both the diagnostic and theragnostic field: from technical aspects (such as semi-automatization of tumor segmentation, image reconstruction, and interpretation) to clinical outcomes, improving a deeper understanding of the molecular environment of PCa, refining personalized treatment strategies, and increasing the ability to predict the outcome. This systematic review aims to describe the current literature on AI and radiomics applied to molecular imaging of prostate cancer.

Artificial intelligence applications in medical imaging: A review of the medical physics research in Italy.

PURPOSE: To perform a systematic review on the research on the application of artificial intelligence (AI) to imaging published in Italy and identify its fields of application, methods and results. MATERIALS AND METHODS: A Pubmed search was conducted using terms Artificial Intelligence, Machine Learning, Deep learning, imaging, and Italy as affiliation, excluding reviews and papers outside time interval 2015-2020. In a second phase, participants of the working group AI4MP on Artificial Intelligence of the Italian Association of Physics in Medicine (AIFM) searched for papers on AI in imaging. RESULTS: The Pubmed search produced 794 results. 168 studies were selected, of which 122 were from Pubmed search and 46 from the working group. The most used imaging modality was MRI (44%) followed by CT(12%) ad radiography/mammography (11%). The most common clinical indication were neurological diseases (29%) and diagnosis of cancer (25%). Classification was the most common task for AI (57%) followed by segmentation (16%). 65% of studies used machine learning and 35% used deep learning. We observed a rapid increase of research in Italy on artificial intelligence in the last 5 years, peaking at 155% from 2018 to 2019. CONCLUSIONS: We are witnessing an unprecedented interest in AI applied to imaging in Italy, in a diversity of fields and imaging techniques. Further initiatives are needed to build common frameworks and databases, collaborations among different types of institutions, and guidelines for research on AI.

Impact of missing attenuation and scatter corrections on 99m Tc-MAA SPECT 3D dosimetry for liver radioembolization using the patient relative calibration methodology: A retrospective investigation on clinical images.

PURPOSE: To investigate the clinical implication of performing pre-treatment dosimetry for 90 Y-microspheres liver radioembolization on 99m Tc-MAA SPECT images reconstructed without attenuation or scatter correction and quantified with the patient relative calibration methodology. METHODS: Twenty-five patients treated with SIR-Spheres® at Istituto Europeo di Oncologia and 31 patients treated with TheraSphere® at Istituto Nazionale Tumori were considered. For each acquired 99m Tc-MAA SPECT, four reconstructions were performed: with attenuation and scatter correction (AC_SC), only attenuation (AC_NoSC), only scatter (NoAC_SC) and without corrections (NoAC_NoSC). Absorbed dose maps were calculated from the activity maps, quantified applying the patient relative calibration to the SPECT images. Whole Liver (WL) and Tumor (T) regions were drawn on CT images. Injected Liver (IL) region was defined including the voxels receiving absorbed dose >3.8 Gy/GBq. Whole Healthy Liver (WHL) and Healthy Injected Liver (HIL) regions were obtained as WHL = WL - T and HIL = IL - T. Average absorbed dose to WHL and HIL were calculated, and the injection activity was derived following each Institute's procedure. The values obtained from AC_NoSC, NoAC_SC and NoAC_NoSC images were compared to the reference value suggested by AC_SC images using Bland-Altman analysis and Wilcoxon paired test (5% significance threshold). Absorbed-dose maps were compared to the reference map (AC_SC) in global terms using the Voxel Normalized Mean Square Error (%VNMSE), and at voxel level by calculating for each voxel the normalized difference with the reference value. The uncertainty affecting absorbed dose at voxel level was accounted for in the comparison; to this purpose, the voxel counts fluctuation due to Poisson and reconstruction noise was estimated from SPECT images of a water phantom acquired and reconstructed as patient images. RESULTS: NoAC_SC images lead to activity prescriptions not significantly different from the reference AC_SC images; the individual differences (<0.1 GBq for all IEO patients, <0.6 GBq for all but one INT patients) were comparable to the uncertainty affecting activity measurement. AC_NoSC and NoAC_NoSC images, instead, yielded significantly different activity prescriptions and wider 95% confidence intervals in the Bland-Altman analysis. Concerning the absorbed dose map, AC_NoSC images had the smallest %VNMSE value and the highest fraction of voxels differing less than 2 standard deviations from AC_SC. CONCLUSIONS: The patient relative calibration methodology can compensate for the missing attenuation correction when performing healthy liver pre-treatment dosimetry: safe treatments can be planned even on NoAC_SC images, suggesting activities comparable to AC_SC images. Scatter correction is recommended due to its heavy impact on healthy liver dosimetry.

The Italian multicentre dosimetric study for lesion dosimetry in 223Ra therapy of bone metastases: Calibration protocol of gamma cameras and patient eligibility criteria.

PURPOSE: The aims of this work were to explore patient eligibility criteria for dosimetric studies in 223Ra therapy and evaluate the effects of differences in gamma camera calibration procedures into activity quantification. METHODS: Calibrations with 223Ra were performed with four gamma cameras (3/8-inch crystal) acquiring planar static images with double-peak (82 and 154keV, 20% wide) and MEGP collimator. The sensitivity was measured in air by varying activity, source-detector distance, and source diameter. Transmission curves were measured for attenuation/scatter correction with the pseudo-extrapolation number method, varying the experimental setup. 223Ra images of twenty-five patients (69 lesions) were acquired to study the lesions visibility. Univariate ROC analysis was performed considering visible/non visible lesions on 223Ra images as true positive/true negative group, and using as score value the lesion/soft tissue contrast ratio (CR) derived from 99mTc-MDP WB scan. RESULTS: Sensitivity was nearly constant varying activity and distance (maximum s.d.=2%). Partial volume effects were negligible for object area ⩾960mm2. Transmission curve measurements are affected by experimental setup and source size, leading to activity quantification errors up to 20%. The ROC analysis yielded an AUC of 0.972 and an optimal threshold of CR of 10, corresponding to an accuracy of 92%. CONCLUSION: The minimum calibration protocol requires sensitivity and transmission curve measurements varying the object size, performing a careful procedure standardisation. Lesions with 99mTc-MDP CR higher than 10, not overlapping the GI tract, are generally visible on 223Ra images acquired at 24h after the administration, and possibly eligible for dosimetric studies.

Impact of SPECT corrections on 3D-dosimetry for liver transarterial radioembolization using the patient relative calibration methodology.

PURPOSE: Many centers aim to plan liver transarterial radioembolization (TARE) with dosimetry, even without CT-based attenuation correction (AC), or with unoptimized scatter correction (SC) methods. This work investigates the impact of presence vs absence of such corrections, and limited spatial resolution, on 3D dosimetry for TARE. METHODS: Three voxelized phantoms were derived from CT images of real patients with different body sizes. Simulations of (99m)Tc-SPECT projections were performed with the SIMIND code, assuming three activity distributions in the liver: uniform, inside a "liver's segment," or distributing multiple uptaking nodules ("nonuniform liver"), with a tumoral liver/healthy parenchyma ratio of 5:1. Projection data were reconstructed by a commercial workstation, with OSEM protocol not specifically optimized for dosimetry (spatial resolution of 12.6 mm), with/without SC (optimized, or with parameters predefined by the manufacturer; dual energy window), and with/without AC. Activity in voxels was calculated by a relative calibration, assuming identical microspheres and (99m)Tc-SPECT counts spatial distribution. 3D dose distributions were calculated by convolution with (90)Y voxel S-values, assuming permanent trapping of microspheres. Cumulative dose-volume histograms in lesions and healthy parenchyma from different reconstructions were compared with those obtained from the reference biodistribution (the "gold standard," GS), assessing differences for D95%, D70%, and D50% (i.e., minimum value of the absorbed dose to a percentage of the irradiated volume). γ tool analysis with tolerance of 3%/13 mm was used to evaluate the agreement between GS and simulated cases. The influence of deep-breathing was studied, blurring the reference biodistributions with a 3D anisotropic gaussian kernel, and performing the simulations once again. RESULTS: Differences of the dosimetric indicators were noticeable in some cases, always negative for lesions and distributed around zero for parenchyma. Application of AC and SC reduced systematically the differences for lesions by 5%-14% for a liver segment, and by 7%-12% for a nonuniform liver. For parenchyma, the data trend was less clear, but the overall range of variability passed from -10%/40% for a liver segment, and -10%/20% for a nonuniform liver, to -13%/6% in both cases. Applying AC, SC with preset parameters gave similar results to optimized SC, as confirmed by γ tool analysis. Moreover, γ analysis confirmed that solely AC and SC are not sufficient to obtain accurate 3D dose distribution. With breathing, the accuracy worsened severely for all dosimetric indicators, above all for lesions: with AC and optimized SC, -38%/-13% in liver's segment, -61%/-40% in the nonuniform liver. For parenchyma, D50% resulted always less sensitive to breathing and sub-optimal correction methods (difference overall range: -7%/13%). CONCLUSIONS: Reconstruction protocol optimization, AC, SC, PVE and respiratory motion corrections should be implemented to obtain the best possible dosimetric accuracy. On the other side, thanks to the relative calibration, D50% inaccuracy for the healthy parenchyma from absence of AC was less than expected, while the optimization of SC was scarcely influent. The relative calibration therefore allows to perform TARE planning, basing on D50% for the healthy parenchyma, even without AC or with suboptimal corrections, rather than rely on nondosimetric methods.

A case report of image-based dosimetry of bone metastases with Alpharadin ((223)Ra-dichloride) therapy: inter-fraction variability of absorbed dose and follow-up.

A 70-year-old man affected by bone metastases from castration resistant prostate cancer underwent Alpharadin ((223)Ra-dichloride) therapy (6 administrations of 50 kBq per kg i.v., once every 4 weeks). The inter-fraction variability of the absorbed dose to lesions was evaluated for four injections. Dosimetric assessments were performed following the MIRD approach and a recently published methodology. The mean absorbed dose and standard deviation for 4 lesions [mean (σ %)] were: 434 mGy (15%) and 516 mGy (21%) for the right and left humeral head, 1205 mGy (14%) and 781 mGy (8%) for the right and left glenoid. The estimated total absorbed dose after the whole treatment, considering also the relative-biological effectiveness of alpha particles (RBE = 5), yielded a D RBE range of 13-36 Gy. A good correlation between (99m)Tc and (223)Ra uptake was obtained (R (2) = 0.7613). The tumour-non-tumour (TNT) ratio of 8 lesions (those above, plus 4 additional), monitored by six (99m)Tc-MDP bone scans over a period of about 10 months, evidenced a TNT reduction in two lesions (-42 and -48 %), but in most lesions the TNT remained fairly constant, evidencing that (223)Ra-dichloride therapy tends to prevent further progression of osseous disease, leading to chronicity of the metastatic status.

Dosimetry of bone metastases in targeted radionuclide therapy with alpha-emitting (223)Ra-dichloride.

PURPOSE: Ra-dichloride is an alpha-emitting radiopharmaceutical used in the treatment of bone metastases from castration-resistant prostate cancer. Image-based dosimetric studies remain challenging because the emitted photons are few. The aim of this study was to implement a methodology for in-vivo quantitative planar imaging, and to assess the absorbed dose to lesions using the MIRD approach. METHODS: The study included nine Caucasian patients with 24 lesions (6 humeral head lesions, 4 iliac wing lesions, 2 scapular lesions, 5 trochanter lesions, 3 vertebral lesions, 3 glenoid lesions, 1 coxofemoral lesion). The treatment consisted of six injections (one every 4 weeks) of 50 kBq per kg body weight. Gamma-camera calibrations for (223)Ra included measurements of sensitivity and transmission curves. Patients were statically imaged for 30 min, using an MEGP collimator, double-peak acquisition, and filtering to improve the image quality. Lesions were delineated on (99m)Tc-MDP whole-body images, and the ROIs superimposed on the (223)Ra images after image coregistration. The activity was quantified with background, attenuation, and scatter correction. Absorbed doses were assessed deriving the S values from the S factors for soft-tissue spheres of OLINDA/EXM, evaluating the lesion volumes by delineation on the CT images. RESULTS: In 12 lesions with a wash-in phase the biokinetics were assumed to be biexponential, and to be monoexponential in the remainder. The optimal timing for serial acquisitions was between 1 and 5 h, between 18 and 24 h, between 48 and 60 h, and between 7 and 15 days. The error in cumulated activity neglecting the wash-in phase was between 2 % and 12 %. The mean effective half-life (T 1/2eff) of (223)Ra was 8.2 days (range 5.5-11.4 days). The absorbed dose (D) after the first injection was 0.7 Gy (range 0.2-1.9 Gy. Considering the relative biological effectiveness (RBE) of alpha particles (RBE = 5), D RBE = 899 mGy/MBq (range 340-2,450 mGy/MBq). The percent uptake of (99m)Tc and (223)Ra (activity extrapolated to t = 0) were significantly correlated. CONCLUSION: The feasibility of in vivo quantitative imaging in (223)Ra therapy was confirmed. The lesion uptake of (223)Ra-dichloride was significantly correlated with that of (99m)Tc-MDP. The D RBE to lesions per unit administered activity was much higher than that of other bone-seeking radiopharmaceuticals, but considering a standard administration of 21 MBq (six injections of 50 kBq/kg to a 70-kg patient), the mean cumulative value of D RBE was about 19 Gy, and was therefore in the range of those of other radiopharmaceuticals. The macrodosimetry of bone metastases in treatments with (223)Ra-dichloride is feasible, but more work is needed to demonstrate its helpfulness in predicting clinical outcomes.