Contrast-medium-enhanced digital mammography (CEDM) is an image subtraction technique which might help unmasking lesions embedded in very dense breasts. Previous works have stated the feasibility of CEDM and the imperative need of radiological optimization. This work presents an extension of a former analytical formalism to predict contrast-to-noise ratio (CNR) in subtracted mammograms. The goal is to optimize radiological parameters available in a clinical mammographic unit (x-ray tube anode/filter combination, voltage, and loading) by maximizing CNR and minimizing total mean glandular dose (D(gT)), simulating the experimental application of an iodine-based contrast medium and the image subtraction under dual-energy nontemporal, and single- or dual-energy temporal modalities. Total breast-entrance air kerma is limited to a fixed 8.76 mGy (1 R, similar to screening studies). Mathematical expressions obtained from the formalism are evaluated using computed mammographic x-ray spectra attenuated by an adipose/glandular breast containing an elongated structure filled with an iodinated solution in various concentrations. A systematic study of contrast, its associated variance, and CNR for different spectral combinations is performed, concluding in the proposal of optimum x-ray spectra. The linearity between contrast in subtracted images and iodine mass thickness is proven, including the determination of iodine visualization limits based on Rose's detection criterion. Finally, total breast-entrance air kerma is distributed between both images in various proportions in order to maximize the figure of merit CNR2/D(gT). Predicted results indicate the advantage of temporal subtraction (either single- or dual-energy modalities) with optimum parameters corresponding to high-voltage, strongly hardened Rh/Rh spectra. For temporal techniques, CNR was found to depend mostly on the energy of the iodinated image, and thus reduction in D(gT) could be achieved if the spectral energy of the noniodinated image is decreased and the breast-entrance air kerma is evenly distributed between both acquisitions. Predicted limits, in terms of iodine concentration, are found to guarantee the visualization of common clinical angiogenic concentrations in the breast.

This phantom study simulates contrast-medium-enhanced digital subtraction mammography (CEDM) and compares subtracted image quality and total mean glandular dose for two alternative spectral combinations available in a GE Senographe DS mammography unit. The first choice takes advantage of large iodine attenuation at low photon energies and uses traditionally available spectra (anode/filter combinations Mo/Mo at 25 kV and Rh/Rh at 40 kV, "Mo25-Rh40"). The second choice, selected from a previous analytical optimization, includes harder spectra obtained by adding external filtration to traditional beams (Rh/Rh at 34 kV and Rh/Rh+5 mm of Al at 45 kV, "Rh34-Rh45H"). Individual images of a custom-made phantom containing tubes of various diameters filled with water- or iodine-based contrast agent were acquired with both spectral combinations. The total breast entrance air kerma, considering subtraction of two images, was limited to 8.76 mGy (1 R). The results were compared to predictions obtained through an analytical formalism that assumes noise of stochastic origin. Individual images were evaluated and subtracted under five combinations of temporal and dual-energy modalities. Signal variance analysis in individual raw images showed important contributions of nonstochastic origin, associated with the software applied to raw images, the curved geometry, and strong attenuation of the phantom cylindrical iodine-filled tubes, causing experimental SNR to vary from 2.2 to 0.8 times the predictions from low to high values of SNR. Iodine contrast in the subtracted images was found to be mainly defined by the spectra, independent of exposure, and linearly dependent on the iodine mass thickness. The highest contrast was obtained with the combined dual-energy temporal subtraction with Rh34-Rh45H, its value was 7% larger than the highest value measured with Mo25-Rh40. As expected, temporal modalities (single and dual energy, any spectral choice) led to higher contrast-over-noise ratio (CNR) than nontemporal dual-energy subtraction, the latter being negligibly small with Mo25-Rh40. CNR for 4 mg iodine/cm2 imaged temporally in a dual-energy fashion with Rh34-Rh45H (iodine imaged at high energy) is about 1.7 times the optimum for Mo25-Rh40 (iodine imaged at low energy). Iodine thicknesses needed to fulfill Rose's criterion were 0.78 +/- 0.02 mg iodine/cm2 for Mo25-Rh40 and 0.54 +/- 0.17 mg iodine/cm2 for Rh34-Rh45H, both lower than the proposed biological concentration of iodine in breast tumors after contrast medium administration. Although similar dose levels were obtained with both spectral choices under dual-energy (temporal and nontemporal) subtraction, the dose obtained in single-energy temporal subtraction with the Mo25 spectrum was 1.2 mGy lower than the dose from the modality offering the highest CNR. In all results considered, the spectral choice Mo25-Rh40 was found to represent an interesting alternative to the use of high-energy hardened spectra for CEDM, particularly when performing dynamic studies of the contrast-agent u...

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Purpose: To optimize radiological and clinical parameters for the application of a contrast‐medium‐based subtraction technique in digital mammography and to evaluate its clinical feasibility using a commercial mammography unit without any external or internal hardware modification. Method and Materials: This is a two‐stage project. Firstly, an extension of Lemacks' analytical formalism was implemented in order to maximize contrast‐to‐noise ratios (CNR) in simulated applications of dual‐energy and temporal subtraction modalities, and combinations of them. The formalism was validated by imaging tubular structures with an iodine‐based contrast medium embedded in a PMMA phantom. Once two optimized techniques were defined, calculations were performed to obtain exposure values limiting the total glandular dose to 2.5 mGy in a dynamical study of 1 mask + 3 post‐contrast images. Secondly, these parameters were used to calibrate the gray level in subtracted images as function of contrast medium iodine concentration contained in a multi‐well PMMA‐phantom. Optimized subtraction techniques are being applied in a clinical study which shall include 20 patients. Results: Experimental CNR results surpass Rose's criterion (CNR=5) and validate the predicted advantage of temporal techniques. Dual energy temporal subtraction, with iodine administered in the low energy image arises as the optimum subtraction technique, instead of the predicted advantage of contrast medium administration during the high‐energy acquisition. With respect to the calibration, relations between CNR and iodine concentration were found to be approximately linear beyond 8 mg/ml, although for lower concentrations, CNR is undetectable. Conclusion: The advantage of temporal over dual energy subtraction in terms of CNR has been validated, particularly of dual energy temporal subtraction. Furthermore, concentrations below 8 mg/ml do not satisfy the detection criterion.