Publications

Journal Article

Hoffmeister, Brent K., Grant R. Jenson, Amalia M. Bay, Ann M. Viano, Phyu Sin M. Myat, Cecille Labuda, Grace I. Nehring, Emily E. Bingham, Blake C. Lawler, and Kate E. Hazelwood. In Press. “Fundamental Ultrasonic Properties of Fresh and Formalin Fixed Brain Visualized As Parametric Images”. Ultrasound Med Biol, In Press.

Objective: The brain is a complex organ with multiple tissue types and a complicated morphology of lobes, folds, ventricles and other structures. The goal of this study was to create detailed parametric images of brain tissue before and after formalin fixation for four ultrasonic parameters: speed of sound (SOS), frequency slope of attenuation (FSA), integrated backscatter coefficient (IBC) and apparent integrated backscatter (AIB).

Methods: Twenty-three, 1-cm thick slices of slices of brain tissue were prepared from the sagittal and coronal planes of nine bovine brains. Ultrasonic measurements were performed using an immersion scanning system equipped with a 5 MHz focused transducer moved in 615 mm steps.

Results: Measured values, reported as mean ± standard deviation averaged over all measurements on all specimens of fresh tissue, were (1535 ± 2) m/s for SOS, (0.546 ± 0.037) dB/cm/MHz for FSA, (0.402 ± 0.165) × 10-3cm-1 str-1 for IBC and (-60.1 ± 1.1) dB for AIB measured relative to a planar glass reflector. Regions of white matter were characterized by higher values of SOS and FSA, and lower values of AIB and IBC. Formalin fixation caused up to a 0.6% increase in SOS, up to a 2% increase in AIB, up to a 20% increase in FSA and up to a 55% increase in IBC averaged over all measurements on all specimens.

Conclusion: Tissue structures and white matter were clearly distinguishable in most parametric images. Formalin fixation caused small to moderate changes in all four ultrasonic parameters.

Labuda, Cecille, Blake C Lawler, Brent K Hoffmeister, Shona C Harbert, Ann M Viano, and Phyu Sin M Myat. (2023) 2023. “Ultrasonic Characterization of Human Scalp”. Ultrasound Med Biol 49 (12). https://doi.org/10.1016/j.ultrasmedbio.2023.08.012.

Objective: The ultrasonic properties of scalp may be relevant to a variety of applications including transcranial ultrasound. However, there is no information about the ultrasonic properties of scalp available in the literature. While ultrasonic studies of skin from other anatomic regions have been previously reported, scalp tissue is generally thicker with a higher density of hair follicles, blood vessels and sebaceous glands. Thus, it is unknown if the ultrasonic properties of scalp are similar to skin from other regions. The goal of this study was to measure the ultrasonic properties of human scalp.

Methods: Pulse-echo measurements were performed with a 7.5 MHz ultrasound transducer to determine the speed of sound (SOS), frequency slope of attenuation (FSA) and integrated backscatter coefficient (IBC) of 32 specimens of formalin-fixed human scalp from four donors.

Results: The means ± standard deviations for these three ultrasonic quantities measured in the frequency range 2.83-7.74 MHz over all specimens were SOS = 1525 ± 16.92 m/s, FSA = 2.59 ± 0.724 dB/cm/MHz and IBC = 0.122 ± 0.0746 cm-1 Sr-1.

Conclusion: These values are comparable to reported values for human skin from other parts of the body, but some differences in SOS and IBC exist.

Keywords: Attenuation; Backscatter; Human scalp; Speed of sound; Ultrasonic properties.

Labuda, Cecille, Will R. Newman, Brent K. Hoffmeister, and Claudia K.M. Chambliss. (2022) 2022. “Two-Dimensional Mapping of the Ultrasonic Attenuation and Speed of Sound in Brain”. Ultrasonics 124. https://doi.org/10.1016/j.ultras.2022.106742.

Brain is inhomogeneous due to its composition of different tissue types (gray and white matter), anatomical structures (e.g. thalamus and cerebellum), and cavities in the brain (ventricles). These inhomogeneities lead to spatial variations in the ultrasonic properties of the organ. The goal of this study is to characterize the spatial variation of the speed of ultrasound and frequency slope of attenuation in fixed sheep brain. 1-cm-thick slices of tissue from the coronal, sagittal and transverse cardinal planes were prepared from 12 brains. Ultrasonic measurements were performed using broadband transducers with center frequencies of 3.5, 5.0, 7.5 and 10 MHz. By mechanically scanning the transducers over the specimens, two-dimensional maps of the speed of sound (SOS) and frequency slope of attenuation (FSA) were produced. Measured values for the spatial mean and standard deviation of FSA ranged between 0.59 and 0.81 dB/cm·MHz and 0.29–0.60 dB/cm·MHz, respectively, depending on the specimen and transducer frequency. Measured values for the spatial mean and standard deviation of SOS ranged from 1532–1541 m/s and 10–14 m/s, respectively. Detailed, two-dimensional maps of FSA and SOS were produced, representing the first such characterization of the spatial variation of the ultrasonic properties of normal mammalian brain.

Dayavansha, E. G. Sunethra K., and Cecille Labuda. (2020) 2020. “Thermal Property and Shear Wave Speed Indicators of Phase Transitions in a Micellar Fluid”. J Acoust Soc Am 147. https://doi.org/10.1121/10.0000945.

High concentration (>100 mM) wormlike micellar (WM) fluids are non-Newtonian with micelle lengths in the tens of nanometers. The viscoelastic properties of the fluid are affected by the structure and entanglement of the micelles and thus structural phase transitions can be indirectly studied using mechanical shear waves. Although these structural phase transitions have been extensively studied as a function of concentration, comparably less work is available on the temperature dependence. In this study, shear wave speeds (SWS) were studied as a function of temperature in a cetyltrimethylammonium bromide (CTAB) and sodium salicylate (NaSal)-based wormlike micellar fluid as an indicator of micellar structural changes. The heat capacity and thermal conductivity were also measured as these can be expected to change with structural phase transitions. Discontinuities in SWS were observed between 12 °C and 14 °C indicating the existence of a possible structural phase transition at this temperature. Gradual variation of the thermal properties was observed during controlled heating and cooling, while during autonomous heating from crystallization to fluid, a dramatic increase in both thermal properties peaking near 13.5 °C was observed.

Taghizadeh, Somayeh, Cecille Labuda, Claus Chunli Yang, Bart Morris, Madhava R. Kanakamedala, Srinivasan Vijayakumar, Roberto Rey-Dios, William N. Duggar, Edward Florez, and Ali Fatemi. 2019. “Optimizing MRI Sequences and Images for MRI-Based Stereotactic Radiosurgery Treatment Planning”. Rep Pract Oncol Radiother 24 (1). https://doi.org/10.1016/j.rpor.2018.09.010.
Aim

Development of MRI sequences and processing methods for the production of images appropriate for direct use in stereotactic radiosurgery (SRS) treatment planning.

Background

MRI is useful in SRS treatment planning, especially for patients with brain lesions or anatomical targets that are poorly distinguished by CT, but its use requires further refinement. This methodology seeks to optimize MRI sequences to generate distortion-free and clinically relevant MR images for MRI-only SRS treatment planning.

Materials and methods

We used commercially available SRS MRI-guided radiotherapy phantoms and eight patients to optimize sequences for patient imaging. Workflow involved the choice of correct MRI sequence(s), optimization of the sequence parameters, evaluation of image quality (artifact free and clinically relevant), measurement of geometrical distortion, and evaluation of the accuracy of our offline correction algorithm.

Results

CT images showed a maximum deviation of 1.3mm and minimum deviation of 0.4mm from true fiducial position for SRS coordinate definition. Interestingly, uncorrected MR images showed maximum deviation of 1.2mm and minimum of 0.4mm, comparable to CT images used for SRS coordinate definition. After geometrical correction, we observed a maximum deviation of 1.1mm and minimum deviation of only 0.3mm.

Conclusion

Our optimized MRI pulse sequences and image correction technique show promising results; MR images produced under these conditions are appropriate for direct use in SRS treatment planning.

Taghizadeh, Somayeh, Cecille Pemberton Labuda, and Joel Mobley. 2018. “Development of a Tissue-Mimicking Phantom of the Brain for Ultrasonic Studies”. Ultrasound Med Biol 44 (12). https://doi.org/10.1016/j.ultrasmedbio.2018.08.012.

Constructing tissue-mimicking phantoms of the brain for ultrasonic studies is complicated by the low backscatter coefficient of brain tissue, causing difficulties in simultaneously matching the backscatter and attenuation properties. In this work, we report on the development of a polyvinyl alcohol-based tissue-mimicking phantom with properties approaching those of human brain tissue. Polyvinyl alcohol was selected as the base material for the phantom as its properties can be varied by freeze–thaw cycling, variations in concentration and the addition of scattering inclusions, allowing some independent control of backscatter and attenuation. The ultrasonic properties (including speed of sound, attenuation and backscatter) were optimized using these methods with talc powder as an additive. It was determined that the ultrasonic properties of the phantom produced in this study are best matched to brain tissue in the frequency range 1–3 MHz, indicating its utility for laboratory ultrasonic studies in this frequency range.

Direct Visualization of Shear Waves in Micellar Fluid Using Microspheres”. 2015. J Acoust Soc Am 137. https://doi.org/10.1121/1.4921728.

Wormlike micellar fluids, being viscoelastic, support shear waves. Shear waves in 500 mM CTAB-NaSal micellar fluid were visualized by seeding the fluid with 212–250 μm diameter polyethylene microspheres. This method was compared to visualization through birefringence induced by shear stress in the fluid. Measured shear wave speeds were 733 and 722 mm/s, respectively, for each technique. Particle displacement was a sinusoidal function of time and displacement amplitude decreased quadratically with distance from the source. This supports the possibility of using particle amplitude measurements as a measure of attenuation even at low fluid concentration where birefringence visualization techniques fail.

Church, Charles C., Cecille Labuda, and Kathryn Nightingale. 2015. “A Theoretical Study of Inertial Cavitation from Acoustic Radiation Force Impulse Imaging and Implications for the Mechanical Index”. Ultrasound Med Biol.

The mechanical index (MI) attempts to quantify the likelihood that exposure to diagnostic ultrasound will produce an adverse biological effect by a non-thermal mechanism. The current formulation of the MI implicitly assumes that the acoustic field is generated using the short pulse durations appropriate to B-mode imaging. However, acoustic radiation force impulse (ARFI) imaging employs high-intensity pulses up to several hundred acoustic periods long. The effect of increased pulse durations on the thresholds for inertial cavitation was studied computationally in water, urine, blood, cardiac and skeletal musclebrain, kidney, liver and skin. The results indicate that, although the effect of pulse duration on cavitation thresholds in the three liquids can be considerable, reducing them by, for example, 6%–24% at 1 MHz, the effect on tissue is minor. More importantly, the frequency dependence of the MI appears to be unnecessarily conservative; that is, the magnitude of the exponent on frequency could be increased to 0.75. Comparison of these theoretical results with experimental measurements suggests that some tissues do not contain the pre-existing, optimally sized bubbles assumed for the MI. This means that in these tissues, the MI is not necessarily a strong predictor of the probability of an adverse biological effect.

Labuda, Cecille Pemberton, and Charles C. Church. 2011. “Augmentation of HIFU-Induced Heating With Fibers Embedded in a Phantom”. Ultrasoui 37 (3). https://doi.org/10.1016/j.ultrasmedbio.2010.12.010.

The effect of fibers on the rate of heat deposition in the focal region of high-intensity focused ultrasound (HIFU) beams was investigated. Nylon, stainless steel and copper fibers of diameters 0.23–0.25, 0.33 and 0.51–0.53 mm embedded in a phantom were exposed to HIFU. The total energy deposited was quantified by measuring the volumes of the lesions formed. The average volumes of the lesions normalized to the average volume of control lesions were 1.19 ± 0.19, 1.43 ± 0.19 and 2.67 ± 0.21 for increasing nylon fiber diameter, indicating an augmented rate of heating. The maximum normalized volume of lesions at the metal fibers was 0.655. These results are consistent with the material properties, which suggest that the mechanism is increased acoustic absorption along with reduction of heat loss by the nylon fiber. The study supports the possibility of improving the efficacy of HIFU-induced hemostasis in vivo by use of a specially designed, nylon fiber-based medical appliance. 

Hoffmeister, Brent K, Grant R Jenson, Amalia M Bay, Ann M Viano, Phyu Sin M Myat, Cecille Labuda, Grace I Nehring, Emily E Bingham, Blake C Lawler, and Kate E Hazelwood. (2025) 2025. “Fundamental Ultrasonic Properties of Fresh and Formalin Fixed Brain Visualized As Parametric Images.”. Ultrasound in Medicine & Biology. https://doi.org/10.1016/j.ultrasmedbio.2025.04.020.

OBJECTIVE: The brain is a complex organ with multiple tissue types and a complicated morphology of lobes, folds, ventricles and other structures. The goal of this study was to create detailed parametric images of brain tissue before and after formalin fixation for four ultrasonic parameters: speed of sound (SOS), frequency slope of attenuation (FSA), integrated backscatter coefficient (IBC) and apparent integrated backscatter (AIB).

METHODS: Twenty-three, 1-cm thick slices of brain tissue were prepared from the sagittal and coronal planes of nine bovine brains. Ultrasonic measurements were performed using an immersion scanning system equipped with a 5 MHz focused transducer moved in 615 μm steps.

RESULTS: Measured values, reported as mean ± standard deviation (representing variation between specimen means) averaged over all measurements on all specimens of fresh tissue, were (1535 ± 2) m/s for SOS, (0.546 ± 0.037) dB/cm/MHz for FSA, (0.402 ± 0.165) × 10-3 cm-1 str-1 for IBC and (-60.1 ± 1.1) dB for AIB measured relative to a planar glass reflector. Regions of white matter were characterized by higher values of SOS and FSA, and lower values of AIB and IBC. Formalin fixation caused up to a 0.6% increase in SOS, up to a 2% increase in AIB, up to a 20% increase in FSA and up to a 55% increase in IBC averaged over all measurements on all specimens.

CONCLUSION: Tissue structures and white matter were clearly distinguishable in most parametric images. Formalin fixation produced significant changes in all four ultrasonic parameters.