Implementation of xSPECT, xSPECT bone and Broadquant from literature, clinical survey and innovative phantom study with task-based image quality assessment.

OBJECTIVE: From patient and phantom studies, we aimed to highlight an original implementation process and share a two-years experience clinical feedback on xSPECT (xS), xSPECT Bone (xB) and Broadquant quantification (Siemens) for 99mTc-bone and 177Lu-NET (neuroendocrine tumors) imaging. METHODS: Firstly, we checked the relevance of implemented protocols and Broadquant module on the basis of literature and with a homogeneous phantom study respectively. Then, we described xS and xB behaviours with reconstruction parameters (10i-0mm to 40i-20mm) and optimized the protocols through a blinded survey (7 physicians). Finally, the preferred 99mTc-bone reconstruction was assessed through an IEC NEMA phantom including liquid bone spheres. Conventional SNR, CNR, spatial resolution, Q.%error, and recovery curves; and innovative NPS, TTF and detectability score d' were performed (ImQuest software). We also sought to review the adoption of these tools in clinical routine and showed the potential of quantitative xB in the context of theranostics (Xofigo®). RESULTS: We showed the need of optimization of implemented reconstruction algorithms and pointed out a decay correction particularity with Broadquant. Preferred parameters were 1s-25i-8mm and 1s-25i-5mm for xS/xB-bone and xS-NET imaging respectively. The phantom study highlighted the different image quality especially for the enhanced spatial resolution xB algorithm (1/TTF10%=2.1 mm) and showed F3D and xB shared the best performances in terms of image quality and quantification. xS was generally less efficient. CONCLUSIONS: Qualitative F3D still remains the clinical standard, xB and Broadquant offer challenging perspectives in theranostics. We introduced the potential of innovative metrics for image quality analysis and showed how CT tools should be adapted to fit nuclear medicine imaging.

Predicting subacute hematological toxicity of 177Lu-DOTATATE therapy using healthy organs' uptake on post-treatment quantitative SPECT: A pilot study.

The aim is to investigate the usefulness of 177Lu-DOTA-0-Tyr3-Octreotate (DOTATATE) healthy organs' (spleen, kidneys, bone marrow) standard uptake value for the prediction of subacute hematological toxicity in patients undergoing 177Lu-DOTATATE treatment. All patients referred from January 2021 to May 2022 for 177Lu-DOTATATE treatment were retrospectively screened. For each treatment session, baseline clinical data including age, sex, weight, delay between 177Lu-DOTATATE treatment and last cold somatostatin analogue intake were collected. Mean standardized uptake value (SUVmean) of healthy organs was measured and analyzed by generalized linear mixed effect models. Outcomes (significant decrease of platelets, hemoglobin levels and neutrophils) were assessed 1 month later, considering their within-subject biological coefficient of variation, published by the European Federation of Clinical Chemistry and Laboratory Medicine. A total of 9 patients (33 treatment sessions) were included. No predictive factors were identified for platelet and neutrophil decrease. Splenic SUVmean was found to be a significant predictor of hemoglobin levels decrease. Using an optimal threshold of ≥6.22, derived sensitivity and specificity to predict hemoglobin decrease were 85.7% [46.4; 99.0] and 76.9% [57.5; 89.2] respectively with an accuracy of 82.4%. Although not significantly predictive of hematological toxicity, bone marrow SUVmean and renal SUVmean were correlated with splenic SUVmean. Quantitative single photon emission computed tomography and healthy organs analysis might help to foresee hematological subacute toxicity in patients undergoing 177Lu-DOTATATE treatment and improve patient management.

Comparison of 3 γ-probes for simultaneous iodine-125-seed and technetium-99m breast cancer surgery: NEMA standard characterisation with extended processing.

PURPOSE: Iodine-125 (125I) seeds can be used as landmarks to locate non-palpable breast lesions instead of implanting metal wires. This relatively new technique requires a nuclear probe usually used for technetium-99m (99mTc) sentinel node detection. This study aimed to compare the performances of different probes and valid the feasibility of this technique, especially in the case of simultaneous 125I-seed and 99mTc breast cancer surgery. METHODS: Three probes with different features (SOE-3211, SOE-3214 and GammaSUP-II) were characterised according to the NEMA NU3-2004 standards for a 99mTc source and a 125I-seed. Several tests such as sensitivity, linearity or spatial resolution allowed an objective comparison of their performances. NEMA testing was extended to work on signals discrimination in case of simultaneous detection of two different sources (innovative figure of merit "Shift Index") and to assess the 99mTc scatter fraction, a useful parameter for the improvement of the probes in terms of detector materials and electronic system. RESULTS: Although the GammaSUP-II probe saturated at a lower activity (1.6 MBq at 10 mm depth), it allowed better sensitivity and spatial resolution at the different NEMA tests performed with the 99mTc source (7865 cps/MBq and 15 mm FWHM at 10 mm depth). With the 125I-seed, the GammaSUP-II was the most sensitive probe (3106 cps/MBq at 10 mm depth) and the SOE-3211 probe had the best spatial resolution (FWHM 20 mm at 10 mm depth). The SOE-3214 probe was more efficient on discriminating 125I from 99mTc in case of simultaneous detection. The SOE probes were more efficient concerning 99mTc scatter fraction assessments. The SOE-3211 probe, with overall polyvalent performances, seemed to be an interesting trade-off for detection of both 125I and 99mTc. CONCLUSION: The three probes showed heterogeneous performances but were all suitable for simultaneous 99mTc sentinel node and 125I-seed detection. This study provides an objective and innovative methodology to compare probes performances and then choose the best trade-off regarding their expected use.

RGD-functionalized magnetosomes are efficient tumor radioenhancers for X-rays and protons.

Although chemically synthesized ferro/ferrimagnetic nanoparticles have attracted great attention in cancer theranostics, they lack radio-enhancement efficacy due to low targeting and internalization ability. Herein, we investigated the potential of RGD-tagged magnetosomes, bacterial biogenic magnetic nanoparticles naturally coated with a biological membrane and genetically engineered to express an RGD peptide, as tumor radioenhancers for conventional radiotherapy and proton therapy. Although native and RGD-magnetosomes similarly enhanced radiation-induced damage to plasmid DNA, RGD-magnetoprobes were able to boost the efficacy of radiotherapy to a much larger extent than native magnetosomes both on cancer cells and in tumors. Combined to magnetosomes@RGD, proton therapy exceeded the efficacy of X-rays at equivalent doses. Also, increased secondary emissions were measured after irradiation of magnetosomes with protons versus photons. Our results indicate the therapeutic advantage of using functionalized magnetoparticles to sensitize tumors to both X-rays and protons and strengthen the case for developing biogenic magnetoparticles for multimodal nanomedicine in cancer therapy.

How reliable are ADC measurements? A phantom and clinical study of cervical lymph nodes.

OBJECTIVE: To assess the reliability of ADC measurements in vitro and in cervical lymph nodes of healthy volunteers. METHODS: We used a GE 1.5 T MRI scanner and a first ice-water phantom according to recommendations released by the Quantitative Imaging Biomarker Alliance (QIBA) for assessing ADC against reference values. We analysed the target size effect by using a second phantom made of six inserted spheres with diameters ranging from 10 to 37 mm. Thirteen healthy volunteers were also scanned to assess the inter- and intra-observer reproducibility of volumetric ADC measurements of cervical lymph nodes. RESULTS: On the ice-water phantom, the error in ADC measurements was less than 4.3 %. The spatial bias due to the non-linearity of gradient fields was found to be 24 % at 8 cm from the isocentre. ADC measure reliability decreased when addressing small targets due to partial volume effects (up to 12.8 %). The mean ADC value of cervical lymph nodes was 0.87.10-3 ± 0.12.10-3 mm2/s with a good intra-observer reliability. Inter-observer reproducibility featured a bias of -5.5 % due to segmentation issues. CONCLUSION: ADC is a potentially important imaging biomarker in oncology; however, variability issues preclude its broader adoption. Reliable use of ADC requires technical advances and systematic quality control. KEY POINTS: • ADC is a promising quantitative imaging biomarker. • ADC has a fair inter-reader variability and good intra-reader variability. • Partial volume effect, post-processing software and non-linearity of scanners are limiting factors. • No threshold values for detecting cervical lymph node malignancy can be drawn.

Quality control in cone-beam computed tomography (CBCT) EFOMP-ESTRO-IAEA protocol (summary report).

The aim of the guideline presented in this article is to unify the test parameters for image quality evaluation and radiation output in all types of cone-beam computed tomography (CBCT) systems. The applications of CBCT spread over dental and interventional radiology, guided surgery and radiotherapy. The chosen tests provide the means to objectively evaluate the performance and monitor the constancy of the imaging chain. Experience from all involved associations has been collected to achieve a consensus that is rigorous and helpful for the practice. The guideline recommends to assess image quality in terms of uniformity, geometrical precision, voxel density values (or Hounsfield units where available), noise, low contrast resolution and spatial resolution measurements. These tests usually require the use of a phantom and evaluation software. Radiation output can be determined with a kerma-area product meter attached to the tube case. Alternatively, a solid state dosimeter attached to the flat panel and a simple geometric relationship can be used to calculate the dose to the isocentre. Summary tables including action levels and recommended frequencies for each test, as well as relevant references, are provided. If the radiation output or image quality deviates from expected values, or exceeds documented action levels for a given system, a more in depth system analysis (using conventional tests) and corrective maintenance work may be required.

4D numerical observer for lesion detection in respiratory-gated PET.

PURPOSE: Respiratory-gated positron emission tomography (PET)/computed tomography protocols reduce lesion smearing and improve lesion detection through a synchronized acquisition of emission data. However, an objective assessment of image quality of the improvement gained from respiratory-gated PET is mainly limited to a three-dimensional (3D) approach. This work proposes a 4D numerical observer that incorporates both spatial and temporal informations for detection tasks in pulmonary oncology. METHODS: The authors propose a 4D numerical observer constructed with a 3D channelized Hotelling observer for the spatial domain followed by a Hotelling observer for the temporal domain. Realistic (18)F-fluorodeoxyglucose activity distributions were simulated using a 4D extended cardiac torso anthropomorphic phantom including 12 spherical lesions at different anatomical locations (lower, upper, anterior, and posterior) within the lungs. Simulated data based on Monte Carlo simulation were obtained using geant4 application for tomographic emission (GATE). Fifty noise realizations of six respiratory-gated PET frames were simulated by GATE using a model of the Siemens Biograph mMR scanner geometry. PET sinograms of the thorax background and pulmonary lesions that were simulated separately were merged to generate different conditions of the lesions to the background (e.g., lesion contrast and motion). A conventional ordered subset expectation maximization (OSEM) reconstruction (5 iterations and 6 subsets) was used to obtain: (1) gated, (2) nongated, and (3) motion-corrected image volumes (a total of 3200 subimage volumes: 2400 gated, 400 nongated, and 400 motion-corrected). Lesion-detection signal-to-noise ratios (SNRs) were measured in different lesion-to-background contrast levels (3.5, 8.0, 9.0, and 20.0), lesion diameters (10.0, 13.0, and 16.0 mm), and respiratory motion displacements (17.6-31.3 mm). The proposed 4D numerical observer applied on multiple-gated images was compared to the conventional 3D approach applied on the nongated and motion-corrected images. RESULTS: On average, the proposed 4D numerical observer improved the detection SNR by 48.6% (p < 0.005), whereas the 3D methods on motion-corrected images improved by 31.0% (p < 0.005) as compared to the nongated method. For all different conditions of the lesions, the relative SNR measurement (Gain = SNRObserved/SNRNongated) of the 4D method was significantly higher than one from the motion-corrected 3D method by 13.8% (p < 0.02), where Gain4D was 1.49 ± 0.21 and Gain3D was 1.31 ± 0.15. For the lesion with the highest amplitude of motion, the 4D numerical observer yielded the highest observer-performance improvement (176%). For the lesion undergoing the smallest motion amplitude, the 4D method provided superior lesion detectability compared with the 3D method, which provided a detection SNR close to the nongated method. The investigation on a structure of the 4D numerical observer showed that a Laguerre-Gaussian channel matrix with a volumetric 3D function yielded higher lesion-detection performance than one with a 2D-stack-channelized function, whereas a different kind of channels that have the ability to mimic the human visual system, i.e., difference-of-Gaussian, showed similar performance in detecting uniform and spherical lesions. The investigation of the detection performance when increasing noise levels yielded decreasing detection SNR by 27.6% and 41.5% for the nongated and gated methods, respectively. The investigation of lesion contrast and diameter showed that the proposed 4D observer preserved the linearity property of an optimal-linear observer while the motion was present. Furthermore, the investigation of the iteration and subset numbers of the OSEM algorithm demonstrated that these parameters had impact on the lesion detectability and the selection of the optimal parameters could provide the maximum lesion-detection performance. The proposed 4D numerical observer outperformed the other observers for the lesion-detection task in various lesion conditions and motions. CONCLUSIONS: The 4D numerical observer shows substantial improvement in lesion detectability over the 3D observer method. The proposed 4D approach could potentially provide a more reliable objective assessment of the impact of respiratory-gated PET improvement for lesion-detection tasks. On the other hand, the 4D approach may be used as an upper bound to investigate the performance of the motion correction method. In future work, the authors will validate the proposed 4D approach on clinical data for detection tasks in pulmonary oncology.