Breast cancer may manifest as microcalcifications (microCs) in x-ray mammography. However, the detection and visualization of microCs are often obscured by the overlapping tissue structures. The dual-energy subtraction imaging technique offers an alternative approach for imaging and visualizing microCs. With this technique, separate high- and low-energy images are acquired and their differences are used to "cancel" out the background tissue structures. However, the subtraction process could increase the statistical noise level relative to the calcification contrast. Therefore, a key issue with the dual-energy subtraction imaging technique is to weigh the benefit of removing the cluttered background tissue structure over the drawback of reduced signal-to-noise ratio in the subtracted microC images. In this report, a theoretical framework for calculating the (quantum) noise in the subtraction images is developed and the numerical computations are described. We estimate the noise levels in the dual-energy subtraction signals under various imaging conditions, including the x-ray spectra, microC size, tissue composition, and breast thickness. The selection of imaging parameters is optimized to evaluate the feasibility of using a dual-energy subtraction technique for the improved detection and visualization of microCs. We present the results and discuss its dependence on imaging parameters.

Radioembolization is an established treatment for chemoresistant and unresectable liver cancers. Currently, treatment planning is often based on semi-empirical methods, which yield acceptable toxicity profiles and have enabled the large-scale application in a palliative setting. However, recently, five large randomized controlled trials using resin microspheres failed to demonstrate a significant improvement in either progression-free survival or overall survival in both hepatocellular carcinoma and metastatic colorectal cancer. One reason for this might be that the activity prescription methods used in these studies are suboptimal for many patients.In this review, the current dosimetric methods and their caveats are evaluated. Furthermore, the current state-of-the-art of image-guided dosimetry and advanced radiobiological modeling is reviewed from a physics’ perspective. The current literature is explored for the observation of robust dose-response relationships followed by an overview of recent advancements in quantitative image reconstruction in relation to image-guided dosimetry.This review is concluded with a discussion on areas where further research is necessary in order to arrive at a personalized treatment method that provides optimal tumor control and is clinically feasible.

Mammographic images of small calcifications, which are often the earliest signs of breast cancer, can be obscured by overlapping fibroglandular tissue. We have developed and implemented a dual-energy digital mammography (DEDM) technique for calcification imaging under full-field imaging conditions using a commercially available aSi:H/CsI:Tl flat-panel based digital mammography system. The low- and high-energy images were combined using a nonlinear mapping function to cancel the tissue structures and generate the dual-energy (DE) calcification images. The total entrance-skin exposure and mean-glandular dose from the low- and high-energy images were constrained so that they were similar to screening-examination levels. To evaluate the DE calcification image, we designed a phantom using calcium carbonate crystals to simulate calcifications of various sizes (212-425 microm) overlaid with breast-tissue-equivalent material 5 cm thick with a continuously varying glandular-tissue ratio from 0% to 100%. We report on the effects of scatter radiation and nonuniformity in x-ray intensity and detector response on the DE calcification images. The nonuniformity was corrected by normalizing the low- and high-energy images with full-field reference images. Correction of scatter in the low- and high-energy images significantly reduced the background signal in the DE calcification image. Under the current implementation of DEDM, utilizing the mammography system and dose level tested, calcifications in the 300-355 microm size range were clearly visible in DE calcification images. Calcification threshold sizes decreased to the 250-280 microm size range when the visibility criteria were lowered to barely visible. Calcifications smaller than approximately 250 microm were usually not visible in most cases. The visibility of calcifications with our DEDM imaging technique was limited by quantum noise, not system noise.

Breast cancer may manifest as microcalcifications in x-ray mammography. Small microcalcifications, essential to the early detection of breast cancer, are often obscured by overlapping tissue structures. Dual-energy imaging, where separate low- and high-energy images are acquired and synthesized to cancel the tissue structures, may improve the ability to detect and visualize microcalcifications. Transmission measurements at two different kVp values were made on breast-tissue-equivalent materials under narrow-beam geometry using an indirect flat-panel mammographic imager. The imaging scenario consisted of variable aluminum thickness (to simulate calcifications) and variable glandular ratio (defined as the ratio of the glandular-tissue thickness to the total tissue thickness) for a fixed total tissue thickness--the clinical situation of microcalcification imaging with varying tissue composition under breast compression. The coefficients of the inverse-mapping functions used to determine material composition from dual-energy measurements were calculated by a least-squares analysis. The linear function poorly modeled both the aluminum thickness and the glandular ratio. The inverse-mapping functions were found to vary as analytic functions of second (conic) or third (cubic) order. By comparing the model predictions with the calibration values, the root-mean-square residuals for both the cubic and the conic functions were approximately 50 microm for the aluminum thickness and approximately 0.05 for the glandular ratio.

The GE Discovery MI PET/CT system has a modular digital detector design allowing three, four, or five detector block rings that extend the axial field-of-view (FOV) from 15 to 25 cm in 5 cm increments. This study investigated the performance of the 5-ring system and compared it to 3-and 4-ring systems; the GE Discovery IQ system that uses conventional photomultiplier tubes; and the GE Signa PET/MR system that has a reduced transaxial FOV. Methods: PET performance was evaluated at three different institutions. Spatial resolution, sensitivity, counting rate performance, accuracy, and image quality were measured in accordance with National Electrical Manufacturers Association NU 2-2012 standards. The mean energy resolution, mean timing resolution, and PET/CT subsystem alignment were also measured. Phantoms were used to determine the effects of varying acquisition time and reconstruction parameters on image quality. Retrospective patient scans were reconstructed with various scan durations to evaluate the impact on image quality. Results: Results from all three institutions were similar. Radial/tangential/axial full width at half maximum spatial resolution measurements using the filtered back projection algorithm were 4.3/4.3/ 5.0 mm, 5.5/4.6/6.5 mm, and 7.4/5.0/6.6 mm at 1, 10, and 20 cm from the center of the FOV, respectively. Measured sensitivity at the center of the FOV (20.84 cps/kBq) was significantly higher than systems with reduced axial FOV. The peak noise-equivalent counting rate was 266.3 kcps at 20.8 kBq/ml, with a corresponding scatter fraction of 40.2%. The correction accuracy for count losses up to the peak noise-equivalent counting rate was 3.6%. For the 10-, 13-, 17-, 22-, 28-, and 37mm spheres, contrast recoveries in the image quality phantom were measured to be 46.2%, 54.3%, 66.1%, 71.1%, 85.3%, and 89.3%, respectively. The mean energy and timing resolution were 9.55% and 381.7 ps, respectively. Phantom and patient images demonstrated excellent image quality, even at short acquisition times or low injected activity. Conclusion: Compared to other PET/CT models, the extended axial FOV improved the overall PET performance of the 5-ring GE Discovery MI scanner. This system offers the potential to reduce scan times or injected activities through increased sensitivity.

Dual-energy digital mammography (DEDM), where separate low- and high-energy images are acquired and synthesized to cancel the tissue structures, may improve the ability to detect and visualize microcalcifications. Under ideal imaging conditions, when the mammography image data are free of scatter and other biases, DEDM could be used to determine the thicknesses of the imaged calcifications. We present quantitative evaluation of a DEDM technique for calcification imaging. The phantoms used in the evaluation were constructed by placing aluminium strips of known thicknesses (to simulate calcifications) across breast-tissue-equivalent materials of different glandular-tissue compositions. The images were acquired under narrow-beam geometry and high exposures to suppress the detrimental effects of scatter and random noise. The measured aluminium thicknesses were found to be approximately linear with the true aluminium thicknesses and independent of the underlying glandular-tissue composition. However, the dual-energy images underestimated the true aluminium thickness due to the presence of scatter from adjacent regions. Regions in the DEDM image that contained no aluminium yielded very low aluminium thicknesses (<0.07 mm). The aluminium contrast-to-noise ratio in the dual-energy images increased with the aluminium thickness and decreased with the glandular-tissue composition. The changes to the aluminium contrast-to-noise ratio and the contrast of the tissue structures between the low-energy and DEDM images are also presented.

We have previously developed a dual-energy digital mammography (DEDM) technique for calcification imaging under full-field imaging conditions using a commercially available flat-panel based digital mammography system. Although dual-energy (DE) imaging could suppress the obscuration of calcifications by tissue-structure background, it also increases the intrinsic noise in the DE images. Here we report on the effects of three different noise reduction techniques on DE calcification images: a simple smoothing (boxcar) filter applied to the DE image, a median filter applied to the HE image prior to the computation of the DE image and an adaptation of the Kalender's correlated-noise reduction (KNR) technique for DEDM. We compared the different noise reduction techniques by evaluating their effects on DE calcification images of a 5 cm thick breast-tissue-equivalent slab with continuously varying glandular-tissue ratio superimposed with calcium carbonate crystals of various sizes that simulate calcifications. Evaluations of different noise reducing techniques were performed by comparison of the root-mean-square signal in background regions (no calcifications present) of the DE calcification images and the contrast-tonoise ratios (CNR) of the calcifications in the DE calcification images. Amongst the different noise reduction techniques evaluated in this study, the KNR method was found to be most effective in reducing the image noise and increasing the calcification visibility (or CNR), closely followed by the HE median filter technique. Although the simple smoothing (boxcar) filter reduced the noise, it did not improve calcification visibility. The visible calcification threshold size with DEDM over smoothly varying background at screening mammography doses, assuming a CNR threshold of 4, was estimated to be around 250 μm with both the HE median filter and the KNR techniques. The quality of DE images with noise reduction techniques based on phantom studies were verified with DE images of an animal-tissue phantom that consisted of calcifications superimposed over more realistic tissue structures.

Purpose To investigate the relationships between tumor absorbed dose (TAD) or normal tissue absorbed dose (NTAD) and clinical outcomes in hepatocellular carcinoma (HCC) treated with yttrium-90 glass microspheres. Methods TARGET was a retrospective investigation in 13 centers across eight countries. Key inclusion criteria: liver-dominant HCC with or without portal vein thrombosis, < 10 tumors per lobe (at least one ≥ 3 cm), Child–Pugh stage A/B7, BCLC stages A–C, and no prior intra-arterial treatment. Multi-compartment pre-treatment dosimetry was performed retrospectively. Primary endpoint was the relationship between ≥ grade 3 hyperbilirubinemia (such that > 15% of patients experienced an event) without disease progression and NTAD. Secondary endpoints included relationships between (1) objective response (OR) and TAD, (2) overall survival (OS) and TAD, and (3) alpha fetoprotein (AFP) and TAD. Results No relationship was found between NTAD and ≥ grade 3 hyperbilirubinemia, which occurred in 4.8% of the 209 patients. The mRECIST OR rate over all lesions was 61.7%; for the target (largest) lesion, 70.8%. Responders and non-responders had geometric mean total perfused TADs of 225.5 Gy and 188.3 Gy (p = 0.048). Probability of OR was higher with increasing TAD (p = 0.044). Higher TAD was associated with longer OS (HR per 100 Gy increase = 0.83, 95% CI: 0.71–0.95; p = 0.009). Increased TAD was associated with higher probability of AFP response (p = 0.046 for baseline AFP ≥ 200 ng/mL). Conclusion Real-world data confirmed a significant association between TAD and OR, TAD and OS, and TAD and AFP response. No association was found between ≥ grade 3 hyperbilirubinemia and NTAD. Trial registration number NCT03295006.