Ultra-high-resolution photon-counting detector computed tomography of the lungs: Phantom and clinical assessment of radiation dose and image quality.

PURPOSE: Photon-counting-detector computed tomography (PCD-CT) offers enhanced noise reduction, spatial resolution, and image quality in comparison to energy-integrated-detectors CT (EID-CT). These hypothesized improvements were compared using PCD-CT ultra-high (UHR) and standard-resolution (SR) scan-modes. METHODS: Phantom scans were obtained with both EID-CT and PCD-CT (UHR, SR) on an adult body-phantom. Radiation dose was measured and noise levels were compared at a minimum achievable slice thickness of 0.5 mm for EID-CT, 0.2 mm for PCD-CT-UHR and 0.4 mm for PCD-CT-SR. Signal-to-noise ratios (SNR) and contrast-to-noise ratios (CNR) were calculated for five tissue densities. Additionally, data from 25 patients who had PCD-CT of chest were reconstructed at 1 mm and 0.2 mm (UHR) slice-thickness and compared quantitatively (SNR) and qualitatively (noise, quality, sharpness, bone details). RESULTS: Phantom PCD-CT-UHR and PCD-CT-SR scans had similar measured radiation dose (16.0mGy vs 15.8 mGy). Phantom PCD-CT-SR (0.4 mm) had lower noise level in comparison to EID-CT (0.5 mm) (9.0HU vs 9.6HU). PCD-CT-UHR (0.2 mm) had slightly higher noise level (11.1HU). Phantom PCD-CT-SR (0.4 mm) had higher SNR in comparison to EID-CT (0.5 mm) while achieving higher resolution (Bone 115 vs 96, Acrylic 14 vs 14, Polyethylene 11 vs 10). SNR was slightly lower across all densities for PCD-CT UHR (0.2 mm). Interestingly, CNR was highest in the 0.2 mm PCD-CT group; PCD-CT CNR was 2.45 and 2.88 times the CNR for 0.5 mm EID-CT for acrylic and poly densities. Clinical comparison of SNR showed predictably higher SNR for 1 mm (30.3 ± 10.7 vs 14.2 ± 7, p = 0.02). Median subjective ratings were higher for 0.2 mm UHR vs 1 mm PCD-CT for nodule contour (4.6 ± 0.3 vs 3.6 ± 0.1, p = 0.02), bone detail (5 ± 0 vs 4 ± 0.1, p = 0.001), image quality (5 ± 0.1 vs 4.6 ± 0.4, p = 0.001), and sharpness (5 ± 0.1 vs 4 ± 0.2). CONCLUSION: Both UHR and SR PCD-CT result in similar radiation dose levels. PCD-CT can achieve higher resolution with lower noise level in comparison to EID-CT.

Development of a 99mTc-Labeled Single-Domain Antibody for SPECT/CT Assessment of HER2 Expression in Breast Cancer.

Accurate determination of human epidermal growth factor receptor 2 (HER2) expression is essential for HER2-targeted therapy in patients with cancer. HER2 expression in a complex environment, such as in a heterogeneous tumor, makes the precise assessment of the HER2 status difficult using current methods. In this study, we developed a novel 99mTc-labeled anti-HER2 single-domain antibody (99mTc-NM-02) as a molecular imaging tracer for the noninvasive detection of HER2 expression and investigated its safety, radiation dosimetry, biodistribution, and tumor-targeting potential in 10 patients with breast cancer. Our data showed that no drug-related adverse reactions occurred. The tracer mainly accumulated in the kidneys and liver with mild uptake in the spleen, intestines, and thyroid; however, only background tracer levels were observed in other organs where primary tumors and metastases typically occurred. The mean effective dose was 6.56 × 10-3 mSv/MBq, and tracer uptake was visually observed in the primary tumors and metastases. A maximal standard uptake value of 1.5 was determined as a reasonable cutoff for identifying HER2 positivity using SPECT/CT imaging. Our 99mTc-NM-02 tracer is safe for use in breast cancer imaging, with reasonable radiation doses, favorable biodistribution, and imaging characteristics. 99mTc-NM-02 SPECT imaging may be an accurate and noninvasive method to detect the HER2 status in patients with breast cancer.

Estimation of absorbed radiation doses to skin and S-values for organs at risk due to nasal administration of PET agents using Monte Carlo simulations.

PURPOSE: The intranasal (IN) administration of radiopharmaceuticals is of interest in being a viable route for the delivery of radiopharmaceuticals that do not ordinarily cross the blood-brain barrier (BBB). However, to be viable in a patient population, good image quality as well as safety of the administration should be demonstrated. This work provides radiation dosimetry calculations and simulations related to the radiation safety of performing such experiments in a human cohort. METHODS: We performed Monte Carlo (MC) simulations to estimate radiation dose to the skin inside a cylindrical model of the nasal cavity assuming a homogenous distribution layer of 11 C and 18 F and calculated a geometry conversion factor (FP-C ) which can be used to convert from a planar geometry to a cylindrical geometry using more widely available software tools. We compared radiation doses from our simulated cylindrical geometry with the planar dose estimates employing our geometry conversion factor from VARSKIN 6.1 software and also from an analytical equation. Furthermore, in order to estimate radiation dosimetry to surrounding organs of interest, we performed a voxelized MC simulation of a fixed radioactivity inside the nasal cavity and calculated S-values to organs such as the eyes, thyroid, and brain. RESULTS: MC simulations of contamination scenarios using planar absorbed doses of 15.50 and 8.60 mGy/MBq for 18 F and 11 C, respectively, and 35.70 and 19.80 mGy/MBq per hour for cylindrical geometries, leading to determination of an FP-C of 2.3. Planar absorbed doses (also in units of mGy/MBq) determined by the analytical equation were 16.96 and 8.68 (18 F and 11 C) and using VARSKIN were 16.60 and 9.26 (18 F and 11 C), respectively. Application of FP-C to these results demonstrates values with a maximum difference of 9.41% from the cylindrical geometry MC calculation, demonstrating that when accounting for geometry, more simplistic techniques can be utilized to estimate IN dosimetry. Voxelized MC simulations of radiation dosimetry from a fixed source of 1 MBq of activity confined to the nasal cavity resulted in S-values to the thyroid, eyes, and brain of 1.72 x 10-6 , 1.93 x 10-5 , and 3.51 x 10-6  mGy/MBq·s, respectively, for 18 F and 1.80 × 10-6 , 1.95 × 10-5 , and 3.54 × 10-6  mGy/MBq·s for 11 C. CONCLUSION: Dosimetry concerns about IN administrations of PET radiotracers should be considered before clinical use. Values presented in the simulations such as the S-values can be further used for assessment of absorbed doses in cases of IN administration, and can be used to develop and adapt specific study protocols. All three presented methods provided similar results when considering the use of a geometry conversion factor for planar to cylindrical geometry, demonstrating that standard tools rather than dedicate MC simulations may be used to perform dose calculations in nasal administrations.

Early Phase I Study of a 99mTc-Labeled Anti-Programmed Death Ligand-1 (PD-L1) Single-Domain Antibody in SPECT/CT Assessment of PD-L1 Expression in Non-Small Cell Lung Cancer.

Immunotherapy with checkpoint inhibitor programmed cell death 1 (PD-1)/programmed death ligand-1 (PD-L1) antibodies demonstrates improvements in treatment of advanced non-small cell lung cancer. Treatment stratification depends on immunohistochemical PD-L1 measurement of biopsy material, an invasive method that does not account for spatiotemporal heterogeneity. Using a single-domain antibody, NM-01, against PD-L1, radiolabeled site-specifically with 99mTc for SPECT imaging, we aimed to assess the safety, radiation dosimetry, and imaging characteristics of this radiopharmaceutical and correlate tumor uptake with PD-L1 immunohistochemistry results. Methods: Sixteen patients (mean age, 61.7 y; 11 men) with non-small cell lung cancer were recruited. Primary tumor PD-L1 expression was measured by immunohistochemistry. NM-01 was radiolabeled with [99mTc(OH2)3(CO)3]+ complex binding to its C-terminal hexahistidine tag. Administered activity was 3.8-10.4 MBq/kg, corresponding to 100 µg or 400 µg of NM-01. Whole-body planar and thoracic SPECT/CT scans were obtained at 1 and 2 h after injection in all patients, and 5 patients underwent additional imaging at 10 min, 3 h, and 24 h for radiation dosimetry calculations. All patients were monitored for adverse events. Results: No drug-related adverse events occurred in this study. The mean effective dose was 8.84 × 10-3 ± 9.33 × 10-4 mSv/MBq (3.59 ± 0.74 mSv per patient). Tracer uptake was observed in the kidneys, spleen, liver, and bone marrow. SPECT primary tumor-to-blood-pool ratios (T:BP) varied from 1.24 to 2.3 (mean, 1.79) at 1 h and 1.24 to 3.53 (mean, 2.22) at 2 h (P = 0.005). Two-hour primary T:BP ratios correlated with PD-L1 immunohistochemistry results (r = 0.68, P = 0.014). Two-hour T:BP was lower in tumors with ≤1% PD-L1 expression (1.89 vs. 2.49, P = 0.048). Nodal and bone metastases showed tracer uptake. Heterogeneity (>20%) between primary tumor and nodal T:BP was present in 4 of 13 patients. Conclusion: This first-in-human study demonstrates that 99mTc-labeled anti-PD-L1-single-domain antibody SPECT/CT imaging is safe and associated with acceptable dosimetry. Tumor uptake is readily visible against background tissues, particularly at 2 h when the T:BP ratio correlates with PD-L1 immunohistochemistry results.

Is Response Assessment of Breast Cancer Bone Metastases Better with Measurement of 18F-Fluoride Metabolic Flux Than with Measurement of 18F-Fluoride PET/CT SUV?

Our purpose was to establish whether noninvasive measurement of changes in 18F-fluoride metabolic flux to bone mineral (Ki) by PET/CT can provide incremental value in response assessment of bone metastases in breast cancer compared with SUVmax and SUVmeanMethods: Twelve breast cancer patients starting endocrine treatment for de novo or progressive bone metastases were included. Static 18F-fluoride PET/CT scans were acquired 60 min after injection, before and 8 wk after commencing treatment. Venous blood samples were taken at 55 and 85 min after injection to measure plasma 18F-fluoride activity concentrations, and Ki in individual bone metastases was calculated using a previously validated method. Percentage changes in Ki, SUVmax, and SUVmean were calculated from the same index lesions (≤5 lesions) from each patient. Clinical response up to 24 wk, assessed in consensus by 2 experienced oncologists masked to PET imaging findings, was used as a reference standard. Results: Of the 4 patients with clinically progressive disease (PD), mean Ki significantly increased (>25%) in all, SUVmax in 3, and SUVmean in 2. Of the 8 non-PD patients, Ki decreased or remained stable in 7, SUVmax in 5, and SUVmean in 6. A significant mean percentage increase from baseline for Ki, compared with SUVmax and SUVmean, occurred in the 4 patients with PD (89.7% vs. 41.8% and 43.5%, respectively; P < 0.001). Conclusion: After 8 wk of endocrine treatment for bone-predominant metastatic breast cancer, Ki more reliably differentiated PD from non-PD than did SUVmax and SUVmean, probably because measurement of SUV underestimates fluoride clearance by not considering changes in input function.

Assessment of an intermediate reprojection technique transitioning from planar to SPECT radionuclide ventriculography.

BACKGROUND: The technique of SPECT-RNV (radionuclide ventriculography) offers a greater amount of clinically usable data than its planar counterpart (P-RNV). In transitioning from planar to SPECT-only acquisition methodologies, reprojection of the SPECT data can provide a planar dataset which can be used as an interim technique. The aim of this study was to test if reprojected planar images could be used as a surrogate for true planar images in SPECT-only setting. METHODS: We performed SPECT-RNV and P-RNV on 47 patients on traditional sodium iodide (NaI) cameras, determining left ventricular ejection fractions (LVEF) for planar (EFP) and SPECT (EFS) techniques. We reprojected the SPECT-RNV data along the best septal separation angle determined from planar scanning. This creates a further planar dataset denoted 'reprojected P-RNV' (rP-RNV) giving a reprojected ejection fraction (EFR) which can be used as a validation variable in transitioning to SPECT-only acquisition. RESULTS: Performing t tests showed no statistical difference between EFP and EFR (P > .017) but bias was observed in EFS results compared to EFP and EFS compared to EFR results. An unblinded, comparison of parametric data between the three datasets for a subset of ten patients showed good clinical concordance. False negative and false positive rates were low for rP-RNV compared to P-RNV. CONCLUSIONS: The reprojected planar LVEF correlates well to P-RNV EF values. The rP-RNV dataset can aid clinicians in transitioning from planar RNV to SPECT-only acquisition.

Three dosimetry models of lipoma arborescens treated by 90Y synovectomy.

PURPOSE: Lipoma arborescens (LA) is a benign intra-articular lipomatous proliferation of the synovial membrane. This extremely rare condition has previously been treated by intra-articular (90)Y radiosynoviorthesis but dosimetry literature on this form of radionuclide therapy is nonexistent. The authors detail methodology for successful treatment of LA and provide for the first time estimates of radiation dosimetry. The authors also analyze the biodistribution of the radiopharmaceutical over the course of the patient's treatment through sequential imaging. METHODS: A patient with bilateral LA underwent intracavity injection of (90)Y citrate colloid to the right and left knee joint spaces (181 and 198 MBq, respectively). SPECT/CT datasets were acquired over 9 days to quantify the biodistribution and kinetics of the radiopharmaceutical. Radiation dosimetry was performed using the MIRD schema (through OLINDA software), a custom voxel-based method, and a direct Monte Carlo calculation (OEDIPE). RESULTS: Follow-up MRI showed marked reduction in LA size in both knees. Mean absorbed doses to the LA were 21.2 ± 0.8 and 42.9 ± 2.3 Gy using OLINDA, 8.1 ± 0.3 and 16.7 ± 0.5 Gy using voxel based methodology, and 8.2 ± 0.3 and 15.7 ± 0.5 Gy for OEDIPE in the right and left LA, respectively. Distribution of the radiopharmaceutical within the joint space alters over the imaging period, with less than 1% of the remaining activity having moved posteriorly in the knee cavity. No uptake was detected outside of the joint space after assessment with whole-body scintigraphy. CONCLUSIONS: An activity of approximately 185 MBq successfully relieved clinical symptoms of LA. There was good correlation between direct Monte Carlo and voxel based techniques, but OLINDA was shown to overestimate the absorbed dose to the tumor. Accurate dosimetry may help select an activity more tailored to the specific size and location of the LA.

Correcting for possible tissue distortion between provocation and assessment in skin testing: the divergent beam UVB photo-test.

BACKGROUND: In tissue viability imaging (TiVi), an assessment method for skin erythema, correct orientation of skin position from provocation to assessment optimizes data interpretation. Image processing algorithms could compensate for the effects of skin translation, torsion and rotation realigning assessment images to the position of the skin at provocation. METHODS: A reference image of a divergent, UVB phototest was acquired, as well as test images at varying levels of translation, rotation and torsion. Using 12 skin markers, an algorithm was applied to restore the distorted test images to the reference image. RESULTS: The algorithm corrected torsion and rotation up to approximately 35 degrees. The radius of the erythemal reaction and average value of the input image closely matched that of the reference image's 'true value'. CONCLUSION: The image 'de-warping' procedure improves the robustness of the response image evaluation in a clinical research setting and opens the possibility of the correction of possibly flawed images performed away from the laboratory setting by the subject/patient themselves. This opportunity may increase the use of photo-testing and, by extension, other late response skin testing where the necessity of a return assessment visit is a disincentive to performance of the test.

The importance of scatter correction for the assessment of lung shunting prior to yttrium-90 radioembolization therapy.

BACKGROUND: Treatment of inoperable hepatocellular carcinoma or secondary metastases by radioembolization using yttrium-90 (90Y) microspheres is a promising method for the treatment of unresectable liver metastases. A pretreatment scintigraphy planar scan using 99mTc-labelled macroaggregated albumin (99mTc-MAA) injected directly into the hepatic artery is carried out to assess the degree of portal shunting of blood between the liver and the lungs. The quantitative results of this scan are used to modulate the activity of therapeutic 90Y microspheres injected into the patient to limit the radiation dose received by the lungs. The presence of scattered events in the MAA lung shunt scan leads to an overestimation of the true shunting ratio, which in turn leads to the administered therapeutic activity being lowered unnecessarily to comply with the protocols of radiation protection. Overall, this may impact the efficacy of treatment. MATERIALS AND METHODS: This study analyses the impact of a window-based analytical scatter-correction method on lung shunt analysis using an anthropomorphic torso phantom, and retrospectively analysed three patient case studies. RESULTS: Our results of scatter in the phantom show a marked decrease in the lung shunt percentage. Clinical analysis of patient data shows that the lung shunt percentage can be overestimated by up to 50% in clinical cases, and depending on the lung shunt percentage, the efficacy of treatment by therapeutic dose reduction may be compromised. CONCLUSION: Our results indicate that scatter correction should be used on 90Y pretreatment 99mTc-MAA scans in order to more accurately assess the lung shunting percentage before therapy.

Tissue viability imaging (TiVi) in the assessment of divergent beam UV-B provocation.

In routine clinical phototesting and in basic research, naked eye dermatological assessment is the "gold standard" for determining the patient's minimal erythemal dose (MED). In UV-B testing with a divergent, radially attenuating beam of characterised dosimetry, laser Doppler perfusion imaging has been previously used to give quantitative description of reactivity to doses above the MED in addition to a "single-dose" objective determination of the MED itself. In the present paper, the recently developed tissue viability imaging (TiVi) technology is presented for the first time as a reliable, easily applicable, high-resolution alternative to LDPI in the divergent beam testing concept. Data obtained after provocation with a range of doses was analysed in order to determine the reaction diameter, which can be related to the MED using field dosimetry. The dose-response features of exposure above the MED and the relationship between naked eye readings and the diameter were determined from the image data. TiVi data were obtained faster than LDPI data and at a higher spatial resolution of 100 µm instead of 1 mm. A tool was developed to centre over the erythema area of the acquired image. Response data could be plotted continuously against dose. Thresholding of processed images compared to naked eye "gold standard" readings showed that the normal skin value +4 standard deviations produced a good fit between both methods. A linear fitting method for the dose-response data provided a further method of determination of the reaction diameter (MED). Erythemal "volume under the surface (VUS)" for the reaction provided a new concept for visualising information. TiVi offers advantages over LDPI in the acquisition and analysis of data collected during divergent beam testing. An increased amount of data compared to traditional phototesting is easily and more objectively obtained which increases applicability in the clinical and research environment.

Sub-epidermal imaging using polarized light spectroscopy for assessment of skin microcirculation.

BACKGROUND/AIMS: Many clinical conditions that affect the microcirculation of the skin are still diagnosed and followed up by observational methods alone in spite of the fact that non-invasive, more user-independent and objective methods are available today. Limited portability, high cost, lack of robustness and non-specificity of findings are among the factors that have hampered the implementation of these methods in a clinical setting. The aim of this study is to present and evaluate a new, portable and easy-to-use imaging technology for investigation of the red blood cell (RBC) concentration in the skin microvasculature based on the method of polarization light spectroscopy using modified standard digital camera technology. METHODS: The use of orthogonal linear polarization filters over both the flash source and the detector array removes the polarization-retaining light reflected from the epidermal layer. Only the depolarized light backscattered from the papillary dermal matrix reaches the detector array. By separating the RGB color planes of an image acquired in this manner and applying a dedicated image processing algorithm, spectroscopic information about the chromophores in the dermal tissue can be attained. If the algorithm is based on a differential principle in which the normalized differences between the individual values of the red and green color plane are calculated, tissue components with similar spectral signature in both planes are suppressed, while components with different spectral signatures such as RBCs are enhanced. RESULTS: In vitro fluid models compare well with theory and computer simulations in describing a linear relationship between the imager output signal termed the tissue viability index (TiVi(index)) and RBC concentration in the physiological range of 0-4% RBC fraction of tissue volume (cc=0.997, n=20). The influence of oxygen saturation on the calculated RBC concentration is limited to within -3.9% for values within the physiological range (70-100% oxygen saturation). Monte Carlo simulations provide information about the sampling depth (about 0.5 mm on the average) of the imaging system. In vivo system evaluation based on iontophoresis of acetylcholine displays a heterogeneous pattern of vasodilatation appearing inside the electrode area after about 10 min. Topical application of methyl nicotinate and clobetasol propionate further demonstrates the capacity to document the extent and intensity of both an increase (erythema) and a decrease (blanching) in the skin RBC concentration without movement artifact and with compensation for irregularity in pigmentation. CONCLUSIONS: Polarization light spectroscopy imaging for assessment of RBC concentration in the skin microvasculature is a robust and accessible technique for the clinical setting. Additionally, the technique has pre-clinical research applications for investigation of the spatial and temporal aspects of skin erythema and blanching as well as a potential role in drug development, skin care product development and skin toxicological assessment.