UltraVision Corporation is developing a new mode of imaging; we call MC-mode to image microcalcifications and calcifications. Like Doppler and Elastography, this new mode involves transmitting a unique type of pulse pattern and then using a unique method of processing the returned echoes from the transducer to form an image. MC-mode is based on the difference in the acoustic impedance between tissue and calcifications which are hard particles.
Acoustic impedance (Z) is a physical property of the material (tissue) that the sound is passing through. It is a measure of how much resistance an ultrasound beam encounters as it passes through the matter. Acoustic impedance depends on the density of the material (d) and the speed of the sound wave through the material (c). They are related by Z = d x c . The acoustic impedance of tissue is around 1.6-1.7 (x 106 kg/(m2s)) (Rayl). A calcium particle has an acoustic impedance of 8-20 ( 106 kg/(m2s).
The amount of reflection that occurs is a function of these acoustic impedances and is called the reflection fraction and is defined by the acoustic impedances of the two materials in the equasion [(Z2 – Z1) / (Z2 + Z1)]2. In short, the reflections that make up B-mode images utilize reflections between tissues and are usually less than 1% of the transmitted energy but the reflection at a calcification can be up to 80% of the incident transmit energy because the acoustic impedances are so different. Thus calcifications appear as strong white dots on a B-mode image. To attain a cosmetic grayscale image the strong echoes are processed with a logarithmic filter so the calcifications are lost in any echogenic volume with the tissue. Many researchers have tried to improve the imaging of microcalcifications but as the calcification gets smaller the easier it is lost in the tissue backscatter, and the results so far have been disappointing.
Our motivation was to visualize microcalcifications in the breast that are found in over 40% of breast cancer patients and these to be of diagnostic significance are less than 0.5 of a millimeter across and so are called microcalcifications (MCs).
We at UltraVision did not look at the power of the reflection but we looked at the power that was transferred to the calcification and we found that the microcalcifications were displaced (i.e. moved). A 150-micron MCs moves up to 5-microns. The MCs are held in place by bindings to the tissue that return the MCs to their original position in 2-3-microseconds.
A standard medical ultrasound scanner uses wave frequencies of 2-20 MHz it is a challenge to detect a particle’s movement of less than 10% of the wavelength of the acoustic pulses so the receive processing could not be just the summed amplitude like in B-mode. We also wanted to use a frequency of about 7-MHz so we could penetrate the breast to the ribs and this has a wavelength of about 220 microns.
So we sent out a transmit pulse of 4 cycles of seven megahertz (which we have found to be optimal). Looking at this from the microcalcifications point of view it has been hit by a pulse so it moves and rotates while it is still moving and rotating it is hit again, and so will move again, and again and again in different directions defined by forces that …….
The forces on the MCs that generate its movement will be based on: a) the direction of the acoustic pulse, b) the angle of incidence to the MCs surface which is not perfectly spherical, c) The MCs bindings to the tissue which will also may not be assumed to be isotropic.
This asymetry will cause displacement momentum and angular momentum so each time the MCs is hit the MCs may be assumed to move in a different direction and each time the MCs is hit it will send out a strong echo back to the transducer but as this path length will be different which creates a signature of that interaction. So we continue collecting the acoustic line data with a digitization every 25-nanoseconds for 70-millimeters (or 100-microseconds). Then we transmit the same four-cycle packet in the same direction and collect an identical acoustic line of data and we subtract the two acoustic lines and the only differences will be at the MCs as their movement due to the multiple pushes was chaotic.
If we subtract the two acoustic lines, we can see a difference but only in the locations where we had a movement. This difference is only visible where something moved, and in the 100 microseconds between sending out the two transmissions, the only thing that moved was the MCs.
We actually plot the acceleration of the MCs on the MC-mode so we have all other movement by blood flow and breathing removed to get an optimal signal to noise.
We also unexpectently found kidney stones at 75-mm depth that were over 2-mm in diameter. So we assume that the larger stone subtends more acoustic lines and also moved several microns. We have found in phantoms MCs down to 45-microns so the high signal to noise seems to compensate for size.
Microcalcifications (MCs), detected by mammography breast screening, are responsible for finding 90% of Ductal Carcinoma In Situ (DCIS) cases, which is an early form of cancer. Further, the description of the morphology and distribution of the microcalcifications as defined in the BI-RADS Atlas* indicates the risk of malignancy.
MCs associated with cancer are small rounded crystals of calcium hydroxyapatite (HA) less than 500-microns across that absorb radiation and appear as white flecks in mammography and are present in about half of breast malignancies. The morphology of the MCs is a significant indicator of the probability of the presence of cancer. Currently, MCs are only reliably seen by mammography, which is an X-ray technique.
Calcium oxalate MCs (Type 1 ) is also present in the breast and appears to be a reliable criterion in favor of the benign nature of a lesion. Calcium hydroxyapatite MCs (HA or Type II) is analogous to bone, induces mitogenesis and upregulation of gene expression, and occurs in benign and malignant lesions. Mammography cannot distinguish Type I MCs from Type II MCs.
In B-mode (grayscale) ultrasound, MCs send large echoes back to the transducer and are also seen as white dots. These dots, however, are easily obscured in the hyper-acoustic areas in breast tissue and can not be reliably detected.
A significant amount of research has been carried out to detect MCs in the breast by ultrasonic methods by many researchers motivated by it is low-cost, real-time, no ionizing radiation, and it can be used on a patient of any age as often as required. So far, however, all methods have failed due to complexity and low signal to noise. MC-mode has a very high signal to noise as demonstrated below.
An engineer at UltraVision Corporation discovered this unique method of reliably detecting MCs. The algorithm has been well tested in phantoms with clusters of 50-200 micron diameter Type II MCs mixed with scatterers (corn starch), and it returns only the strong signals only from the MCs. The algorithm has also found every MCs implanted in chicken breast and pork breasts.
So far, the method has no false positives and has detected every known MCs either in a breast or placed in a phantom.
In a different breast, we again find three MCs in a cyst.
Figure 3 shows a patient with implants where the implant was replaced because of silicon leakage over ten years ago. The replacement has now developed MCs on its surface. In the contralateral breast, no leakage occurred, and MCs have not been found.
The next goal of our research is to differentiate the types of MCs by their acoustic impedances and densities, from 40-200 microns in diameter.
In the extremely magnified image immediately below of a phantom with one Type I and one Type II microcalcification we see both particles.
Again at the same point in the phantom we can change the processing and remove the Type I (calcium oxalate particle, not associated with cancer).
Again changing parameters we can remove the Type II (calcium hydroxyapatite, Associated with cancer).
Anyone having an interest in participating with our MC-mode research, is urged to contact us.
Remarkably a mode designed to detect small less than 200-micron particles shows 2-mm plus stones with a curved linear transducer at 75 mm depth in a patient.
And in a younger engineer on our team we find a small stone.
Carotid Artery Plaque