Nebojsa Duric

Detection of breast cancer with ultrasound tomography: First results with the Computed Ultrasound Risk Evaluation (CURE) prototype

Although mammography is the gold standard for breast imaging, its limitations result in a high rate of biopsies of benign lesions and a significant false negative rate for women with dense breasts. In response to this imaging performance gap we have been developing a clinical breast imaging methodology based on the principles of ultrasound tomography. The Computed Ultrasound Risk Evaluation (CURE) system has been designed with the clinical goals of whole breast, operator-independent imaging, and differentiation of breast masses. This paper describes the first clinical prototype, summarizes our initial image reconstruction techniques, and presents phantom and preliminary in vivo results. In an initial assessment of its in vivo performance, we have examined 50 women with the CURE prototype and obtained the following results. (1) Tomographic imaging of breast architecture is demonstrated in both CURE modes of reflection and transmission imaging. (2) In-plane spatial resolution of 0.5 mm in reflection and 4 mm in transmission is achieved. (3) Masses > 15 mm in size are routinely detected. (4) Reflection, sound speed, and attenuation imaging of breast masses are demonstrated. These initial results indicate that operator-independent, whole-breast imaging and the detection of breast masses are feasible. Future studies will focus on improved detection and differentiation of masses in support of our long-term goal of increasing the specificity of breast exams, thereby reducing the number of biopsies of benign masses.

In vivo Breast Sound-Speed Imaging with Ultrasound Tomography

We discuss a bent-ray ultrasound tomography algorithm with total-variation (TV) regularization. We have applied this algorithm to 61 in vivo breast datasets collected with our in-house clinical prototype for imaging sound-speed distributions in the breast. Our analysis showed that TV regularization could preserve sharper lesion edges than the classic Tikhonov regularization. Furthermore, the image quality of our TV bent-ray sound-speed tomograms was superior to that of the straight-ray counterparts for all types of breasts within BI-RADS density categories 1 through 4. Our analysis showed that the improvements for average sharpness (in the unit of (m x s)(-1)) of lesion edges in our TV bent-ray tomograms are between 2.1 to 3.4-fold compared with the straight ray tomograms. Reconstructed sound-speed tomograms illustrated that our algorithm could successfully image fatty and glandular tissues within the breast. We calculated the mean sound-speed values for fatty tissue and breast parenchyma as 1422 +/- 9 m/s (mean +/- SD) and 1487 +/- 21 m/s, respectively. Based on 32 lesions in a cohort of 61 patients, we also found that the mean sound-speed for malignant breast lesions (1548 +/- 17 m/s) was higher, on average, than that of benign ones (1513 +/- 27 m/s) (one-sided p<0.001). These results suggest that, clinically, sound-speed tomograms can be used to assess breast density (and therefore, breast cancer risk), as well as detect and help differentiate breast lesions. Finally, our sound-speed tomograms may also be a useful tool to monitor the clinical response of breast cancer patients to neo-adjuvant chemotherapy.

Development of ultrasound tomography for breast imaging: technical assessment

Ultrasound imaging is widely used in medicine because of its benign characteristics and real-time capabilities. Physics theory suggests that the application of tomographic techniques may allow ultrasound imaging to reach its full potential as a diagnostic tool allowing it to compete with other tomographic modalities such as x-ray computer tomography, and MRI. This paper describes the construction and use of a prototype tomographic scanner and reports on the feasibility of implementing tomographic theory in practice and the potential of ultrasound (US) tomography in diagnostic imaging. Data were collected with the prototype by scanning two types of phantoms and a cadaveric breast. A specialized suite of algorithms was developed and utilized to construct images of reflectivity and sound speed from the phantom data. The basic results can be summarized as follows. (i) A fast, clinically relevant US tomography scanner can be built using existing technology. (ii) The spatial resolution, deduced from images of reflectivity, is 0.4 mm. The demonstrated 10 cm depth-of-field is superior to that of conventional ultrasound and the image contrast is improved through the reduction of speckle noise and overall lowering of the noise floor. (iii) Images of acoustic properties such as sound speed suggest that it is possible to measure variations in the sound speed of 5 m/s. An apparent correlation with x-ray attenuation suggests that the sound speed can be used to discriminate between various types of soft tissue. (iv) Ultrasound tomography has the potential to improve diagnostic imaging in relation to breast cancer detection.

Novel approach to evaluating breast density utilizing ultrasound tomography.

Women with high mammographic breast density have a four- to fivefold increased risk of developing breast cancer compared to women with fatty breasts. Many preventative strategies have attempted to correlate changes in breast density with response to interventions including drugs and diet. The purpose of this work is to investigate the feasibility of assessing breast density with acoustic velocity measurements with ultrasound tomography, and to compare the results with existing measures of mammographic breast density. An anthropomorphic breast tissue phantom was first imaged with our computed ultrasound tomography clinical prototype. Strong positive correlations were observed between sound speed and material density, and sound speed and computed tomography number (Pearson correlation coefficients= 0.87 and 0.91, respectively). A cohort of 48 women was then imaged. Whole breast acoustic velocity was determined by creating image stacks and evaluating the sound speed frequency distribution. The acoustic measures of breast density were evaluated by comparing these results to two mammographic density measures: (1) qualitative estimates determined by a certified radiologist using the BI-RADS Categorical Assessment based on a 1 (fatty) to 4 (dense) scale, and (2) quantitative measurements via digitization and computerized analysis of archival mammograms. A one-way analysis of variance showed that a significant difference existed between the mean values of sound speed according to BI-RADS category, while post hoc analyses using the Scheffé criterion for significance indicated that BI-RADS 4 (dense) patients had a significantly higher sound speed than BI-RADS 1, 2, and 3 at an alpha level of 0.05. Using quantitative measures of breast density, a direct correlation between the mean acoustic velocity and calculated mammographic percent breast density was demonstrated with correlation coefficients ranging from 0.75 to 0.89. The results presented here support the hypothesis that sound speed can be used as an indicator of breast tissue density. Noninvasive, nonionizing monitoring of dietary and chemoprevention interventions that affect breast density are now possible.

An improved automatic time-of-flight picker for medical ultrasound tomography

OBJECTIVE AND MOTIVATION Time-of-flight (TOF) tomography used by a clinical ultrasound tomography device can efficiently and reliably produce sound-speed images of the breast for cancer diagnosis. Accurate picking of TOFs of transmitted ultrasound signals is extremely important to ensure high-resolution and high-quality ultrasound sound-speed tomograms. Since manually picking is time-consuming for large datasets, we developed an improved automatic TOF picker based on the Akaike information criterion (AIC), as described in this paper. METHODS We make use of an approach termed multi-model inference (model averaging), based on the calculated AIC values, to improve the accuracy of TOF picks. By using multi-model inference, our picking method incorporates all the information near the TOF of ultrasound signals. Median filtering and reciprocal pair comparison are also incorporated in our AIC picker to effectively remove outliers. RESULTS We validate our AIC picker using synthetic ultrasound waveforms, and demonstrate that our automatic TOF picker can accurately pick TOFs in the presence of random noise with absolute amplitudes up to 80% of the maximum absolute signal amplitude. We apply the new method to 1160 in vivo breast ultrasound waveforms, and compare the picked TOFs with manual picks and amplitude threshold picks. The mean value and standard deviation between our TOF picker and manual picking are 0.4 micros and 0.29 micros, while for amplitude threshold picker the values are 1.02 micros and 0.9 micros, respectively. Tomograms for in vivo breast data with high signal-to-noise ratio (SNR) ( approximately 25 dB) and low SNR ( approximately 18 dB) clearly demonstrate that our AIC picker is much less sensitive to the SNRs of the data, compared to the amplitude threshold picker. DISCUSSION AND CONCLUSIONS The picking routine developed here is aimed at determining reliable quantitative values, necessary for adding diagnostic information to our clinical ultrasound tomography device--CURE. It has been successfully adopted into CURE, and allows us to generate such values reliably. We demonstrate that in vivo sound-speed tomograms with our TOF picks significantly improve the reconstruction accuracy and reduce image artifacts.

A New Sample of Radio‐selected and Optically Confirmed Supernova Remnants in M33

Using radio data to identify and optical data to confirm, we have established the largest and most complete sample of extragalactic radio-bright supernova remnants (SNRs) in the nearby spiral galaxy M33. We have identified 53 radio SNRs, doubling the size of the earlier survey by Duric et al. The increased sample size provides more insight into the nature of SNRs and provides an extensive informational database about SNRs for future studies. The SNR sample was analyzed for statistical trends that relate to the evolution of their radio emission. We report no significant correlation between the radio flux densities and diameters of SNRs in our sample. The absence of a statistically meaningful Σ-D relation is consistent with the view that environmental factors govern the radio evolution of SNRs. A new radio luminosity function for SNRs is presented. Although there appears to be a break in the function, the break is the result of selection effects and not intrinsic to the sample. A comparison of the radio luminosity function with the integrated radio continuum properties of M33 suggests that SNRs may well be the primary source of the relativistic electrons in M33. A histogram of synchrotron spectral indices of the SNRs is presented. Statistical analysis of the spectral index distribution indicates that the mean spectral index of SNRs in M33 is steeper than the mean in samples of SNRs in the Galaxy or the LMC and is consistent with a particle spectrum expected from a diffusive shock acceleration process.

A New Optical Sample of Supernova Remnants in M33

We present a new and larger sample of supernova remnants in the nearby spiral galaxy M33. The sample is based upon CCD interference filter observations obtained with the Kitt Peak 4 m telescope and spectroscopic observations obtained with the Multiple Mirror Telescope. Using optical emission-line ratios, supplemented by a radio continuum map of M33 (Duric et al.; Gordon et al.), we have identified 98 supernova remnant (SNR) candidates, of which 53 were previously unknown. We have obtained spectra of 27 SNR candidates, bringing the total number of M33 SNRs for which spectra are available to 72. All the spectra show the characteristic signature of shock-heated gas, which leads us to believe that the rest of the candidates are also supernova remnants. The large sample provides a useful database to investigate the global properties of SNRs. In this paper, we present a new cumulative number-diameter [N(<D)] relation for SNRs. We find that the free expansion model is inconsistent with the observed N(<D) relation and that the Sedov-Taylor (ST) expansion model is a much better fit. The ST expansion model is used to derive a SN rate in M33 of one SN every 360 yr. The spectroscopic sample of SNRs is the largest of its kind in any galaxy. Our investigations show no relation between [N II]:Hα and [S II] λ6717:λ6731. We do, however, find weak trends between the SNR diameter and [N II]:Hα and [S II]:Hα. Further, we find a strong correlation between [N II]:Hα and the galactocentric distance (GCD) indicative of an abundance gradient. There is a large dispersion in the [N II]:Hα ratio at a given GCD that cannot be explained by evolutionary effects and that may be due to a larger abundance dispersion in the inner part of the galaxy.

Nuclear, disk-focused wind and the bipolar structure of the spiral galaxy NGC 3079

A high-resolution, radio continuum study of the spiral galaxy NGC 3079 is presented which reveals the presence of a figure eight morphology along the minor axis, centered on the nucleus. The nucleus itself dominates the emission from the galaxy. It has an inverted spectrum and is a possible VLBI source. The morphology is successfully modeled as the interaction between a nuclear wind and interstellar gas in the disk and halo. In this model, the wind plows up interstellar material as it propagates away from the nucleus. The disk focuses the wind along the minor axis, thereby creating the observed features. The restricted volume of space where the wind originates and the high energies associated with the wind point to a compact object such as a black hole or an unusually compact and massive star cluster as the source of the wind. 24 references.

An X-Ray, Optical, and Radio Search for Supernova Remnants in the Nearby Sculptor Group Sd Galaxy NGC 7793

This paper is the second in a series devoted to examining the multiwavelength properties of supernova remnants (SNRs) located in nearby galaxies. We consider here the resident SNRs in the nearby Sculptor group Sd galaxy NGC 7793. Using our own Very Large Array (VLA) radio observations at 6 and 20 cm, as well as archived ROSAT X-ray data, previously published optical results, and our own Hα image, we have searched for X-ray and radio counterparts to previously known optically identified SNRs and for new previously unidentified SNRs at these two wavelength regimes. Consistent with our prior results for NGC 300, only a tiny minority of the optically identified SNRs have been found at another wavelength. The most noteworthy source in our study is N7793-S26, which is the only SNR in this galaxy that is detected at all three wavelengths (X-ray, optical, and radio). It features a long (~450 pc) filamentary morphology that is clearly seen in both the optical and the radio images. N7793-S26s radio luminosity exceeds that of the Galactic SNR Cas A, and based on equipartition calculations we determine that an energy of at least 1052 ergs is required to maintain this source. Such a result argues for the source being created by multiple supernova explosions rather than by a single supernova event. A second optically identified SNR, N7793-S11, has detectable radio emission but no detectable X-ray emission. A radio-selected sample of candidate SNRs has also been prepared by searching for coincidences between nonthermal radio sources and regions of Hα emission in this galaxy. This search has produced five new candidate radio SNRs to be added to the 28 SNRs that have already been detected by optical methods. A complementary search for new candidate X-ray SNRs has also been conducted by searching for soft-spectrum sources (kT < 1 keV) that are coincident with regions of Hα emission. That search has yielded a candidate X-ray SNR that is coincident with one (and possibly two) of the candidate radio SNRs, but considerable diffuse X-ray emission throughout the disk of NGC 7793 reduces the efficacy of the search. Like NGC 300, very little overlap in identifications is seen between the SNRs found through X-ray, optical, and radio methods, and such a result argues for the role played by distance-dependent selection effects in determining the detectability of SNRs. In addition, we find that the density of the ambient interstellar medium (ISM) surrounding SNRs significantly impacts the spectral characteristics of the SNRs in this galaxy, consistent with surveys of the SNR populations in other galaxies.

On the spatial sampling of wave fields with circular ring apertures

This paper investigates the sampling criterion needed to image objects within a circular ring array. The array consists of transducer elements deployed along a circular aperture at regular angular intervals. Each transducer excites waves which propagate towards the center of the array and detects outgoing fields traveling towards it. It is shown that while with conventional linear apertures the sampling criterion is dictated by the wavelength of the probing wave only, in the case of a circular aperture the sampling depends on the size of the object relative to the wavelength and its position with respect to the aperture.