Patient-Reported Outcomes and Predictive Factors following Focused Ultrasound Thalamotomy for Essential Tremor.

INTRODUCTION: The objectives of this study were to determine long-term patient-reported outcomes with magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy for medication-refractory essential tremor (ET) and to identify risk factors for a poor clinical outcome. METHODS: We administered a telephone or mail-in survey to patients who consecutively underwent unilateral MRgFUS thalamotomy for ET at our institution over an 8-year period. Patients were asked to self-report measures of hand tremor improvement, degree of overall postprocedure improvement, activities of daily life, side effects, and willingness to undergo the procedure again. Specific patient characteristics, ultrasound treatment parameters, and postoperative radiological findings from magnetic resonance imaging performed 1 day after the procedure were analyzed, and multivariable linear regression was used to determine if these factors could serve as predictors of clinical outcome. RESULTS: A total of 85 patients were included in this study with a mean follow-up time of 3.0 years (range 2 months to 1 8.4 years). The mean patient-reported improvement in hand tremor at last follow-up was 66%, and 73% of patients reported meaningful change in their overall condition after the procedure. The percentages of patients reporting normal or only minimal limitations with feeding, drinking, and writing ability at last follow-up were 60%, 71%, and 48%, respectively. In the position of their former selves, 89% of patients would again choose to undergo the procedure. Larger lesions were correlated with a higher risk of adverse events. DISCUSSION/CONCLUSION: While subjective hand tremor improvement declines with time, willingness to undergo the procedure again following MRgFUS thalamotomy for ET remains very high even several years after the procedure.

Feasibility and Safety of MR-Guided Focused Ultrasound Lesioning in the Setting of Deep Brain Stimulation.

BACKGROUND: Patients treated with deep brain stimulation (DBS) often develop symptom progression. If safe, focused ultrasound (FUS) lesioning could be used for patients unable to undergo further DBS surgery. OBJECTIVE: To test the feasibility and safety of MR-guided FUS surgery in the setting of a previously implanted DBS system. METHODS: Three preclinical experiments were designed to test feasibility and safety. Hydrogels were implanted with an electrode, and FUS lesions were targeted adjacently. Cadavers were implanted with a thalamic electrode, and FUS lesions were targeted in the contralateral thalamus. Finally, DBS systems were implanted in swine, and FUS lesioning was targeted to the contralateral thalamus, MRI was used to assess the treatments, and histological analyses were performed at 2 days and at 1 month. RESULTS: In gel experiments and cadavers, FUS resulted in target heating to 29-32°C without any heating at the electrode. In animal experiments, there were no FUS-related MRI signal changes near the electrode. Histological analysis showed typical FUS lesions with no evidence of damage surrounding the electrode tracts. CONCLUSIONS: FUS is feasible in the setting of a preimplanted DBS device. There was minimal heating of the device during the procedure and no apparent FUS-related tissue injury. © 2015 S. Karger AG, Basel.

Improving Sonication Efficiency in Transcranial MR-Guided Focused Ultrasound Treatment: A Patient-Data Simulation Study.

The potential improvement in sonication efficiency achieved by tilting the focused ultrasound (FUS) transducer of the transcranial MR-guided FUS system is presented. A total of 56 cases of patient treatment data were used. The relative position of the clinical FUS transducer to the patient's head was reconstructed, and region-specific skull density and porosity were calculated based on the patient's CT volume image. The total transmission coefficient of acoustic waves emitted from each channel was calculated. Then, the total energy penetrating the human skull-which represents the sonication efficiency-was estimated. As a result, improved sonication efficiency was by titling the FUS transducer to a more appropriate angle achieved in all 56 treatment cases. This simulation result suggests the potential improvement in transcranial-focused ultrasound treatment by simply adjusting the transducer angle.

Thermal Neuromodulation With Focused Ultrasound: Implications for the Technique of Subthreshold Testing.

BACKGROUND: During focused ultrasound ablation (FUSA), the presumed stereotactic target is tested with subthreshold sonications before permanent ablation. This testing relies on ultrasound-induced reversible clinical effects (thermal neuromodulation, TN). However, the thermal dose and spot size thresholds to induce TN are not yet defined. OBJECTIVE: To define the thermal dose and spot size thresholds associated with TN. METHODS: We performed a retrospective analysis of intraoperative FUSA data of essential tremor patients. Sonications with a thermal dose of less than 25 cumulative equivalent minutes (CEM) were classified as subthreshold. The intraoperative writing samples were independently rated by 2 raters using the clinical rating scale for tremor. The association between thermal dose and tremor scores was statistically analyzed, and the thermal dose and spot size thresholds for TN were computed using leave-one-out cross-validation analysis. RESULTS: A total of 331 pairs of sonications and writing samples were analyzed; 97 were classified as subthreshold sonications. TN was observed in 23 (24%) subthreshold sonications. The median tremor improvement during TN was 20% (interquartile range = 41.6). The thermal dose threshold for TN was 0.67 CEM (equivalent to 30 s thermal exposure at 43°C). The spot size threshold for TN was 2.46 mm. Ventral intermediate medial nucleus was exposed to TN thermal dose during subablative and ablative sonications. CONCLUSION: The TN thermal dose and spot size thresholds are significantly higher than the current FUSA standard of care. We recommend long duration (>30 s), subthreshold sonications for intraoperative testing during FUSA. Future investigations should test whether the thermal dose threshold is tissue-specific and determine the mechanisms underlying focused ultrasound TN.

Evaluation of Pseudorandom Sonications for Reducing Cavitation With a Clinical Neurosurgery HIFU Device.

Transcranial high-intensity focused ultrasound is used in clinics for treating essential tremor (ET) and proposed for many other brain disorders. This promising treatment modality requires high energy resulting eventually in undesired cavitation and potential side effects. The goals of the present work were: 1) to evaluate the potential increase of the cavitation threshold using pseudorandom gated sonications and 2) to assess the heating capabilities with such sonications. The experiments were performed with the transcranial magnetic resonance (MR)-compatible ExAblate Neuro system (InSightec, Haifa, Israel) operating at a frequency of 670 kHz, either in continuous wave (CW) or with pseudorandom gated sonications of 50% duty cycle. Cavitation activity with the two types of sonications was compared using chemical dosimetry of hydroxyl radical production at the focus of the transducer, after propagation in water or through a human skull. Heating trials were performed in a hydrogel tissue-mimicking material embedded in a human skull to mimic a clinical situation. The temperature was measured by MR-thermometry when focusing at the geometrical focus and steering off focus up to 15 mm. Compared with CW sonications, the use of gated sonication did not affect the efficiency (60%) nor the steering abilities of the transducer. After propagation through a human skull, gated sonication required a higher pressure level (10 MPa) to initiate cavitation as compared with CW (5.8 MPa). Moreover, at equivalent acoustic power above the cavitation threshold, the level of cavitation activity initiated with gated sonications was much lower with gated sonication than with continuous sonications, almost half after propagation through water and one-third after propagation through a skull. This lowered cavitation activity may be attributed to a breaking of the dynamic of the bubbles moving from monochromatic to more broadband sonications and to the removal of residual cavitation nuclei between pulses with gated sonications. The heating capability was not affected by the gated sonications, and similar temperature increases were reached at focus with both types of sonications when sonicating at equivalent acoustic power, both in water or after propagation through a human skull (+15 °C at 325 W for 10 s). These data, acquired with a clinical system, suggest that gated sonication could be an alternative to continuous sonications when cavitation onset is an issue.

Wavelength dependence of sensitivity in spectral diffuse optical imaging: effect of normalization on image reconstruction.

Near Infrared Diffuse Optical Tomography has the potential to be used as a non-invasive imaging tool for biological tissue specifically for the diagnosis and characterization of breast cancer. Most model based reconstruction algorithms rely on calculating and inverting a large Jacobian matrix. Although this method is flexible for a wide range of complex problems, it usually results in large image artifacts from hypersensitivity around the detectors. In this work a Jacobian normalization technique is presented which takes into account the varying magnitude of different optical parameters creating a more uniform update within a spectral image reconstruction model. Using simulated data the Jacobian normalization method is used to reconstructed images of absolute chromophore and scattering parameters which are qualitatively and quantitatively as compared to conventional methods. The hypersensitivity resulting in boundary artifacts are shown to be minimized with only a small additional computational cost.

Wavelength band optimization in spectral near-infrared optical tomography improves accuracy while reducing data acquisition and computational burden.

Multispectral near-infrared (NIR) tomographic imaging has the potential to provide information about molecules absorbing light in tissue, as well as subcellular structures scattering light, based on transmission measurements. However, the choice of possible wavelengths used is crucial for the accurate separation of these parameters, as well as for diminishing crosstalk between the contributing chromophores. While multispectral systems are often restricted by the wavelengths of laser diodes available, continuous-wave broadband systems exist that have the advantage of providing broadband NIR spectroscopy data, albeit without the benefit of the temporal data. In this work, the use of large spectral NIR datasets is analyzed, and an objective function to find optimal spectral ranges (windows) is examined. The optimally identified wavelength bands derived from this method are tested using both simulations and experimental data. It is found that the proposed method achieves images as qualitatively accurate as using the full spectrum, but improves crosstalk between parameters. Additionally, the judicious use of these spectral windows reduces the amount of data needed for full spectral tomographic imaging by 50%, therefore increasing computation time dramatically.

High-resolution high-speed panoramic cardiac imaging system.

A panoramic cardiac imaging system consisting of three high-speed CCD cameras has been developed to image the surface electrophysiology of a rabbit heart via fluorescence imaging using a voltage-sensitive fluorescent dye. A robust, unique mechanical system was designed to accommodate the three cameras and to adapt to the requirements of future experiments. A unified computer interface was created for this application - a single workstation controls all three CCD cameras, illumination, stimulation, and a stepping motor that rotates the heart. The geometric reconstruction algorithms were adapted from a previous cardiac imaging system. We demonstrate the system by imaging a polymorphic cardiac tachycardia.

An efficient Jacobian reduction method for diffuse optical image reconstruction.

Model based image reconstruction in Diffuse Optical Tomography relies on both the numerical accuracy of the forward model as well as the computational speed and efficiency of the inverse model. Most model based image reconstruction algorithms rely on Newton type inversion methods, whereby the inverse of a large Jacobian is approximated. In this work we present an efficient Jacobian reduction method which takes into account the total sensitivity of the imaging domain to the measured boundary data. It is shown using numerical and phantom data that by removing regions within the inverse model whose contribution to the measured data is less than 1%, it has no significant effect upon the estimated inverse problem, but does provide up to a 14 fold improvement in computational time.

Ultrashort echo-time MRI versus CT for skull aberration correction in MR-guided transcranial focused ultrasound: In vitro comparison on human calvaria.

PURPOSE: Transcranial magnetic resonance-guided focused ultrasound (TcMRgFUS) brain treatment systems compensate for skull-induced beam aberrations by adjusting the phase and amplitude of individual ultrasound transducer elements. These corrections are currently calculated based on a preacquired computed tomography (CT) scan of the patient's head. The purpose of the work presented here is to demonstrate the feasibility of using ultrashort echo-time magnetic resonance imaging (UTE MRI) instead of CT to calculate and apply aberration corrections on a clinical TcMRgFUS system. METHODS: Phantom experiments were performed in three ex-vivo human skulls filled with tissue-mimicking hydrogel. Each skull phantom was imaged with both CT and UTE MRI. The MR images were then segmented into "skull" and "not-skull" pixels using a computationally efficient, threshold-based algorithm, and the resulting 3D binary skull map was converted into a series of 2D virtual CT images. Each skull was mounted in the head transducer of a clinical TcMRgFUS system (ExAblate Neuro, Insightec, Israel), and transcranial sonications were performed using a power setting of approximately 750 acoustic watts at several different target locations within the electronic steering range of the transducer. Each target location was sonicated three times: once using aberration corrections calculated from the actual CT scan, once using corrections calculated from the MRI-derived virtual CT scan, and once without applying any aberration correction. MR thermometry was performed in conjunction with each 10-s sonication, and the highest single-pixel temperature rise and surrounding-pixel mean were recorded for each sonication. RESULTS: The measured temperature rises were ∼ 45% larger for aberration-corrected sonications than for noncorrected sonications. This improvement was highly significant (p < 10(-4)). The difference between the single-pixel peak temperature rise and the surrounding-pixel mean, which reflects the sharpness of the thermal focus, was also significantly larger for aberration-corrected sonications. There was no significant difference between the sonication results achieved using CT-based and MR-based aberration correction. CONCLUSIONS: The authors have demonstrated that transcranial focal heating can be significantly improved in vitro by using UTE MRI to compute skull-induced ultrasound aberration corrections. Their results suggest that UTE MRI could be used instead of CT to implement such corrections on current 0.7 MHz clinical TcMRgFUS devices. The MR image acquisition and segmentation procedure demonstrated here would add less than 15 min to a clinical MRgFUS treatment session.

Head phantoms for transcranial focused ultrasound.

PURPOSE: In the ongoing endeavor of fine-tuning, the clinical application of transcranial MR-guided focused ultrasound (tcMRgFUS), ex-vivo studies wlkiith whole human skulls are of great use in improving the underlying technology guiding the accurate and precise thermal ablation of clinically relevant targets in the human skull. Described here are the designs, methods for fabrication, and notes on utility of three different ultrasound phantoms to be used for brain focused ultrasound research. METHODS: Three different models of phantoms are developed and tested to be accurate, repeatable experimental options to provide means to further this research. The three models are a cadaver, a gel-filled skull, and a head mold containing a skull and filled with gel that mimics the brain and the skin. Each was positioned in a clinical tcMRgFUS system and sonicated at 1100 W (acoustic) for 12 s at different locations. Maximum temperature rise as measured by MR thermometry was recorded and compared against clinical data for a similar neurosurgical target. Results are presented as heating efficiency in units (°C/kW/s) for direct comparison to available clinical data. The procedure for casting thermal phantom material is presented. The utility of each phantom model is discussed in the context of various tcMRgFUS research areas. RESULTS: The cadaveric phantom model, gel-filled skull model, and full head phantom model had heating efficiencies of 5.3, 4.0, and 3.9 °C/(kW/s), respectively, compared to a sample clinical heating efficiency of 2.6 °C/(kW/s). In the seven research categories considered, the cadaveric phantom model was the most versatile, though less practical compared to the ex-vivo skull-based phantoms. CONCLUSIONS: Casting thermal phantom material was shown to be an effective way to prepare tissue-mimicking material for the phantoms presented. The phantom models presented are all useful in tcMRgFUS research, though some are better suited to a limited subset of applications depending on the researchers needs.

Focused ultrasound development and clinical adoption: 2013 update on the growth of the field.

The field of therapeutic focused ultrasound, which first emerged in the 1940s, has seen significant growth, particularly over the past decade. The eventual widespread clinical adoption of this non-invasive therapeutic modality require continued progress, in a multitude of activities including technical, pre-clinical, and clinical research, regulatory approval and reimbursement, manufacturer growth, and other commercial and public sector investments into the field, all within a multi-stakeholder environment. We present here a snapshot of the field of focused ultrasound and describe how it has progressed over the past several decades. It is assessed using metrics which include quantity and breadth of academic work (presentations, publications), funding trends, manufacturer presence in the field, number of treated patients, number of indications reaching first-in-human status, and quantity and breadth of clinical indications.

Trans-cranial focused ultrasound without hair shaving: feasibility study in an ex vivo cadaver model.

In preparing a patient for a trans-cranial magnetic resonance (MR)-guided focused ultrasound procedure, current practice is to shave the patient's head on treatment day. Here we present an initial attempt to evaluate the feasibility of trans-cranial focused ultrasound in an unshaved, ex vivo human head model. A human skull filled with tissue-mimicking phantom and covered with a wig made of human hair was sonicated using 220- and 710-kHz head transducers to evaluate the feasibility of acoustic energy transfer. Heating at the focal point was measured by MR proton resonance shift thermometry. Results showed that the hair had a negligible effect on focal spot thermal rise at 220 kHz and a 17% drop in temperature elevation when using 710 kHz.

Potential intracranial applications of magnetic resonance-guided focused ultrasound surgery.

Magnetic resonance-guided focused ultrasound surgery (MRgFUS) has the potential to create a shift in the treatment paradigm of several intracranial disorders. High-resolution MRI guidance combined with an accurate method of delivering high doses of transcranial ultrasound energy to a discrete focal point has led to the exploration of noninvasive treatments for diseases traditionally treated by invasive surgical procedures. In this review, the authors examine the current intracranial applications under investigation and explore other potential uses for MRgFUS in the intracranial space based on their initial cadaveric studies.

Transcranial magnetic resonance-guided focused ultrasound surgery for trigeminal neuralgia: a cadaveric and laboratory feasibility study.

OBJECT: Transcranial MR-guided focused ultrasound surgery (MRgFUS) is evolving as a treatment modality in neurosurgery. Until now, the trigeminal nerve was believed to be beyond the treatment envelope of existing high-frequency transcranial MRgFUS systems. In this study, the authors explore the feasibility of targeting the trigeminal nerve in a cadaveric model with temperature assessments using computer simulations and an in vitro skull phantom model fitted with thermocouples. METHODS: Six trigeminal nerves from 4 unpreserved cadavers were targeted in the first experiment. Preprocedural CT scanning of the head was performed to allow for a skull correction algorithm. Three-Tesla, volumetric, FIESTA MRI sequences were performed to delineate the trigeminal nerve and any vascular structures of the cisternal segment. The cadaver was positioned in a focused ultrasound transducer (650-kHz system, ExAblate Neuro, InSightec) so that the focus of the transducer was centered at the proximal trigeminal nerve, allowing for targeting of the root entry zone (REZ) and the cisternal segment. Real-time, 2D thermometry was performed during the 10- to 30-second sonication procedures. Post hoc MR thermometry was performed on a computer workstation at the conclusion of the procedure to analyze temperature effects at neuroanatomical areas of interest. Finally, the region of the trigeminal nerve was targeted in a gel phantom encased within a human cranium, and temperature changes in regions of interest in the skull base were measured using thermocouples. RESULTS: The trigeminal nerves were clearly identified in all cadavers for accurate targeting. Sequential sonications of 25-1500 W for 10-30 seconds were successfully performed along the length of the trigeminal nerve starting at the REZ. Real-time MR thermometry confirmed the temperature increase as a narrow focus of heating by a mean of 10°C. Postprocedural thermometry calculations and thermocouple experiments in a phantom skull were performed and confirmed minimal heating of adjacent structures including the skull base, cranial nerves, and cerebral vessels. For targeting, inclusion of no-pass regions through the petrous bone decreased collateral heating in the internal acoustic canal from 16.7°C without blocking to 5.7°C with blocking. Temperature at the REZ target decreased by 3.7°C with blocking. Similarly, for midcisternal targeting, collateral heating at the internal acoustic canal was improved from a 16.3°C increase to a 4.9°C increase. Blocking decreased the target temperature increase by 4.4°C for the same power settings. CONCLUSIONS: This study demonstrates focal heating of up to 18°C in a cadaveric trigeminal nerve at the REZ and along the cisternal segment with transcranial MRgFUS. Significant heating of the skull base and surrounding neural structures did not occur with implementation of no-pass regions. However, in vivo studies are necessary to confirm the safety and efficacy of this potentially new, noninvasive treatment.

Minimally invasive treatment of intracerebral hemorrhage with magnetic resonance-guided focused ultrasound.

OBJECT: Intracerebral hemorrhage (ICH) is a major cause of death and disability throughout the world. Surgical techniques are limited by their invasive nature and the associated disability caused during clot removal. Preliminary data have shown promise for the feasibility of transcranial MR-guided focused ultrasound (MRgFUS) sonothrombolysis in liquefying the clotted blood in ICH and thereby facilitating minimally invasive evacuation of the clot via a twist-drill craniostomy and aspiration tube. METHODS AND RESULTS: In an in vitro model, the following optimum transcranial sonothrombolysis parameters were determined: transducer center frequency 230 kHz, power 3950 W, pulse repetition rate 1 kHz, duty cycle 10%, and sonication duration 30 seconds. Safety studies were performed in swine (n = 20). In a swine model of ICH, MRgFUS sonothrombolysis of 4 ml ICH was performed. Magnetic resonance imaging and histological examination demonstrated complete lysis of the ICH without additional brain injury, blood-brain barrier breakdown, or thermal necrosis due to sonothrombolysis. A novel cadaveric model of ICH was developed with 40-ml clots implanted into fresh cadaveric brains (n = 10). Intracerebral hemorrhages were successfully liquefied (> 95%) with transcranial MRgFUS in a highly accurate fashion, permitting minimally invasive aspiration of the lysate under MRI guidance. CONCLUSIONS: The feasibility of transcranial MRgFUS sonothrombolysis was demonstrated in in vitro and cadaveric models of ICH. Initial in vivo safety data in a swine model of ICH suggest the process to be safe. Minimally invasive treatment of ICH with MRgFUS warrants evaluation in the setting of a clinical trial.

Magnetic resonance-guided focused ultrasound surgery: Part 2: A review of current and future applications.

Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a novel combination of technologies that is actively being realized as a noninvasive therapeutic tool for a myriad of conditions. These applications are reviewed with a focus on neurological use. A combined search of PubMed and MEDLINE was performed to identify the key events and current status of MRgFUS, with a focus on neurological applications. MRgFUS signifies a potentially ideal device for the treatment of neurological diseases. As it is nearly real time, it allows monitored provision of treatment location and energy deposition; is noninvasive, thereby limiting or eliminating disruption of normal tissue; provides focal delivery of therapeutic agents; enhances radiation delivery; and permits modulation of neural function. Multiple clinical applications are currently in clinical use and many more are under active preclinical investigation. The therapeutic potential of MRgFUS is expanding rapidly. Although clinically in its infancy, preclinical and early-phase I clinical trials in neurosurgery suggest a promising future for MRgFUS. Further investigation is necessary to define its true potential and impact.

FEA modeling of CMUT with membrane stand-off structures to enable selectable frequency-mode operation.

A selectable, dual-frequency, capacitive micro- machined ultrasonic transducer (CMUT) designed for both high-frequency imaging and low-frequency therapeutic effect is presented. A validated finite element analysis (FEA) CMUT model was used to examine the performance of the proposed dual-frequency transducer. CMUT device simulations were used to design a hybrid device incorporating stand-off structures that divide a large, low-frequency membrane into smaller, high-frequency sub-membranes when the membrane is partially collapsed so that the stand-offs contact the substrate. In low-frequency operation, simulations indicated that the peak negative pressure achieved by the hybrid device, when biased by 30.0 VDC and excited by a 2-MHz signal with 30.0 V amplitude, exceeded 190 kPa, which is sufficient for microbubble rupture. Low-frequency mode bandwidth was 93% at a center frequency of 2.1 MHz. In the high-frequency mode of operation, the device was excited by 175 Vdc and 87.5 Vac, which generated a peak negative pressure of 247 kPa. Device center frequency was 44.1 MHz with a - 6-dB fractional bandwidth of 42%.

Construction of a genetic multiplexer to toggle between chemosensory pathways in Escherichia coli.

Many applications require cells to switch between discrete phenotypic states. Here, we harness the FimBE inversion switch to flip a promoter, allowing expression to be toggled between two genes oriented in opposite directions. The response characteristics of the switch are characterized using two-color cytometry. This switch is used to toggle between orthogonal chemosensory pathways by controlling the expression of CheW and CheW*, which interact with the Tar (aspartate) and Tsr* (serine) chemoreceptors, respectively. CheW* and Tsr* each contain a mutation at their protein-protein interface such that they interact with each other. The complete genetic program containing an arabinose-inducible FimE controlling CheW/CheW* (and constitutively expressed tar/tsr*) is transformed into an Escherichia coli strain lacking all native chemoreceptors. This program enables bacteria to swim toward serine or aspartate in the absence or in the presence of arabinose, respectively. Thus, the program functions as a multiplexer with arabinose as the selector. This demonstrates the ability of synthetic genetic circuits to connect to a natural signaling network to switch between phenotypes.

Filled and unfilled temperature-dependent epoxy resin blends for lossy transducer substrates.

In the context of our ongoing investigation of low-cost 2-dimensional (2-D) arrays, we studied the temperature- dependent acoustic properties of epoxy blends that could serve as an acoustically lossy backing material in compact 2-D array-based devices. This material should be capable of being machined during array manufacture, while also providing adequate signal attenuation to mitigate backing block reverberation artifacts. The acoustic impedance and attenuation of 5 unfilled epoxy blends and 2 filled epoxy blends - tungsten and fiberglass fillers - were analyzed across a 35 degrees C temperature range in 5 degrees C increments. Unfilled epoxy materials possessed an approximately linear variation of impedance and sigmoidal variation of attenuation properties over the range of temperatures of interest. An intermediate epoxy blend was fitted to a quadratic trend line with R(2) values of 0.94 and 0.99 for attenuation and impedance, respectively. It was observed that a fiberglass filler induces a strong quadratic trend in the impedance data with temperature, which results in increased error in the characterization of attenuation and impedance. The tungsten-filled epoxy was not susceptible to such problems because a different method of fabrication was required. At body temperature, the tungsten-filled epoxy could provide a 44 dB attenuation of the round-trip backing block echo in our application, in which the center frequency is 5 MHz and the backing material is 1.1 mm thick. This is an 11 dB increase in attenuation compared with the fiberglass-filled epoxy in the context of our application. This work provides motivation for exploring the use of custom-made tungsten-filled epoxy materials as a substitute PCB-based substrate to provide electrical signal interconnect.