Biomedical subjects

Nadine Barrie Smith

Publications and source records attributed to Nadine Barrie Smith.

8 recordsLinked to original sources

PubMed2006

MR thermometry characterization of a hyperthermia ultrasound array designed using the k-space computational method.

BACKGROUND: Ultrasound induced hyperthermia is a useful adjuvant to radiation therapy in the treatment of prostate cancer. A uniform thermal dose (43 degrees C for 30 minutes) is required within the targeted cancerous volume for effective therapy. This requires specific ultrasound phased array design and appropriate thermometry method. Inhomogeneous, acoustical, three-dimensional (3D) prostate models and economical computational methods provide necessary tools to predict the appropriate shape of hyperthermia phased arrays for better focusing. This research utilizes the k-space computational method and a 3D human prostate model to design an intracavitary ultrasound probe for hyperthermia treatment of prostate cancer. Evaluation of the probe includes ex vivo and in vivo controlled hyperthermia experiments using the noninvasive magnetic resonance imaging (MRI) thermometry. METHODS: A 3D acoustical prostate model was created using photographic data from the Visible Human Project. The k-space computational method was used on this coarse grid and inhomogeneous tissue model to simulate the steady state pressure wavefield of the designed phased array using the linear acoustic wave equation. To ensure the uniformity and spread of the pressure in the length of the array, and the focusing capability in the width of the array, the equally-sized elements of the 4 x 20 elements phased array were 1 x 14 mm. A probe was constructed according to the design in simulation using lead zerconate titanate (PZT-8) ceramic and a Delrin plastic housing. Noninvasive MRI thermometry and a switching feedback controller were used to accomplish ex vivo and in vivo hyperthermia evaluations of the probe. RESULTS: Both exposimetry and k-space simulation results demonstrated acceptable agreement within 9%. With a desired temperature plateau of 43.0 degrees C, ex vivo and in vivo controlled hyperthermia experiments showed that the MRI temperature at the steady state was 42.9 +/- 0.38 degrees C and 43.1 +/- 0.80 degrees C, respectively, for 20 minutes of heating. CONCLUSION: Unlike conventional computational methods, the k-space method provides a powerful tool to predict pressure wavefield in large scale, 3D, inhomogeneous and coarse grid tissue models. Noninvasive MRI thermometry supports the efficacy of this probe and the feedback controller in an in vivo hyperthermia treatment of canine prostate.

Acoustics↗

PubMed2005

A 63 element 1.75 dimensional ultrasound phased array for the treatment of benign prostatic hyperplasia.

BACKGROUND: Prostate cancer and benign prostatic hyperplasia are very common diseases in older American men, thus having a reliable treatment modality for both diseases is of great importance. The currently used treating options, mainly surgical ones, have numerous complications, which include the many side effects that accompany such procedures, besides the invasive nature of such techniques. Focused ultrasound is a relatively new treating modality that is showing promising results in treating prostate cancer and benign prostatic hyperplasia. Thus this technique is gaining more attention in the past decade as a non-invasive method to treat both diseases. METHODS: In this paper, the design, construction and evaluation of a 1.75 dimensional ultrasound phased array to be used for treating prostate cancer and benign prostatic hyperplasia is presented. With this array, the position of the focus can be controlled by changing the electrical power and phase to the individual elements for electronically focusing and steering in a three dimensional volume. The array was designed with a maximum steering angle of +/- 13.5 degrees in the transverse direction and a maximum depth of penetration of 11 cm, which allows the treatment of large prostates. The transducer piezoelectric ceramic, matching layers and cable impedance have been designed for maximum power transfer to tissue. RESULTS: To verify the capability of the transducer for focusing and steering, exposimetry was performed and the results correlated well with the calculated field. Ex vivo experiments using bovine tissue were performed with various lesion sizes and indicated the capability of the transducer to ablate tissue using short sonications. CONCLUSION: A 1.75 dimensional array, that overcame the drawbacks associated with one-dimensional arrays, has been designed, built and successfully tested. Design issues, such as cable and ceramic capacitances, were taken into account when designing this array. The final prototype overcame also the problem of generating grating lobes at unwanted locations by tapering the array elements.

Animals↗

PubMed2005

Glucose measurements with sensors and ultrasound.

Accurate monitoring of the blood glucose level in diabetics is essential in preventing complications. Generally, conventional over-the-counter glucose meters require frequent painful finger punctures to obtain samples, which makes a noninvasive method preferable. The purpose of this study was to demonstrate that glucose levels can be measured transdermally with the combination of the low-profile cymbal array and an electrochemical glucose sensor consisting of amperometric electrodes and a novel glucose oxidase hydrogel. Interstitial fluid glucose concentrations can be determined with the electrochemical glucose sensor after the skin is made permeable to glucose by ultrasound (US) (20 kHz) with the thin (< 7 mm) and light (< 22 g) cymbal array. Using this array to deliver insulin into hyperglycemic rats, our previous experiments demonstrated that blood glucose levels would decrease 233.3 mg/dl with 5 min of US exposure. With the sensor and array, our goal was to determine the glucose levels of hyperglycemic rats noninvasively and evaluate the possible bioeffects. A total of 12 anesthetized rats were placed into two groups (US exposure group and control group) and the array (I(SPTP) = 100 mW/cm(2)) with a saline reservoir operating for 20 min was affixed to the abdomen. The array was removed and an electrochemical glucose sensor was placed on the exposed area to determine the glucose concentrations through the skin. Comparison was made using a commercial glucose meter with the blood collected from a jugular vein. The average blood glucose level determined by the sensor was 356.0 +/- 116.6 mg/dl, and the glucose level measured by the commercial glucose meter was 424.8 +/- 59.1 mg/dl. These results supported the use of this novel system consisting of the electrochemical glucose sensor and the cymbal array for glucose monitoring.

Animals↗

PubMed2004

Noninvasive ultrasonic transdermal insulin delivery in rabbits using the light-weight cymbal array.

OBJECTIVE: Recent studies have shown that ultrasound-mediated transdermal drug delivery offers a promising potential for noninvasive drug administration. The purpose of this study was to demonstrate ultrasonic transdermal delivery of insulin in vivo using rabbits with a novel, low-profile two-by-two ultrasound array based on the cymbal transducer. As a practical device, the cymbal array (f = 20 kHz) was 37 x 37 x 7 mm3 in size and weighed less than 22 g. Using the same array on hyperglycemic rats, our previous experiments demonstrated that blood glucose would decrease 233.3 +/- 22.2 mg/dL in 90 min from 5 min of pulsed ultrasound exposure. With a similar intensity (Isptp = 100 mW/cm2, 20% duty cycle), our goal was to determine if the same effect could be achieved with rabbits. METHODS: Experiments were performed in 16 New Zealand White rabbits (weighing 2.7-3.4 kg) divided into three groups: two controls and one ultrasound with insulin exposure. The rabbits were first anesthetized, and their thigh area was shaved for the exposure area. While the animal was lying in the lateral recumbent position, a 1-mm-thick, water-tight standoff (reservoir) that held insulin or saline was fastened between the thigh and the ultrasound array. The first control group (control 1: insulin-no ultrasound) had insulin placed in the reservoir with no ultrasound exposure, while the second control group (control 2: saline-ultrasound) had saline in the reservoir with ultrasound operating at Isptp = 100 mW/cm2 for 60 min. The third rabbit group (ultrasound-insulin) was subjected to insulin with ultrasound exposure for 60 min (Isptp = 100 mW/cm2). At the beginning of the experiment and every 15 min for 90 min, 0.3 mL of blood was collected from the ear vein to determine the blood glucose level (in mg/dL) using a glucose monitoring system. For comparison between individual rabbits, the change in the blood glucose level was normalized to a baseline value. The insulin reservoir was removed with the array after the ultrasound was turned off at 60 min of exposure. RESULTS: For both controls, insulin-no ultrasound and saline-ultrasound, the blood glucose level varied from the initial baseline by approximately +75 mg/dL. However, for the ultrasound-insulin group, the glucose level was found to decrease to -132.6 +/- 35.7 mg/dL from the initial baseline in 60 min. Even after the array and insulin reservoir were removed, the blood glucose level of ultrasound-insulin group continued to decrease to -208.1 +/- 29 mg/dL from the initial baseline. CONCLUSIONS: These results indicate the feasibility of using a low-cost, lightweight cymbal array for enhanced transdermal insulin delivery using ultrasound.

Administration, Cutaneous↗

PubMed2004

Short ultrasound exposure times for noninvasive insulin delivery in rats using the lightweight cymbal array.

The purpose of this study is to demonstrate the feasibility of using short ultrasound exposure times to noninvasively deliver insulin with a lightweight (<22 g), low-profile (37 x 37 x 7 mm3) cymbal array (f = 20 kHz). Using hyperglycemic rats, previous experiments using the array demonstrated that blood glucose would decrease approximately 250 mg/dl from 60 and 20 minutes of pulsed ultrasound exposure for transdermal insulin delivery. Using a similar intensity (Isptp = 100 mW/cm2, 20% duty cycle), the goal was to determine if the same effect can be achieved with only 5 minutes of ultrasound exposure. For these experiments, 20 Sprague Dawley rats were anesthetized and shaved, and a 1-mm watertight standoff reservoir that held the insulin or saline was placed between the rat's abdomen and the ultrasound array. At the beginning of the experiment and every 30 minutes, 0.3 ml of blood was collected from the jugular vein to determine the blood glucose level (milligrams per deciliter) for a total of 90 minutes. For comparison purposes between the rats, the change in the glucose level for each rat was normalized to a baseline (i.e., 0 mg/dl). The first control group used insulin in the reservoir without any ultrasound. The second control group had saline in the reservoir with ultrasound operating at Isptp = 100 mW/cm2 for 60 minutes. For the noncontrol experiments, the third group used insulin with ultrasound exposure for 10 minutes. The last group used insulin with ultrasound operating with a 5-minute exposure to examine the effects of using short ultrasound exposure times on delivery. For the 10- and 5-minute ultrasound exposure groups, the glucose level was found to decrease from the baseline to -174.6 +/- 67.2 and -200.4 +/- 43.4 mg/dl measured after 1 hour, respectively. These results indicated that ultrasound exposure times do not need to be long to deliver a clinically significant insulin dose to reduce a high blood glucose level.

Administration, Cutaneous↗

PubMed2003

Ultrasound-mediated transdermal transport of insulin in vitro through human skin using novel transducer designs.

Recent studies have shown that ultrasound (US)-mediated transdermal drug delivery offers a promising potential for noninvasive drug administration. The purpose of this study was to improve low-frequency (20 kHz) US methods for enhancing the transport of insulin in vitro across human skin. The feasibility of using US produced by small, lightweight novel transducers was explored for enhancing the transport of insulin across skin. Previous investigators have used US devices such as large, heavy sonicators or commercially obtained transducers for this type of research. The experiments carried out in this study used two low-profile novel US transducer arrays, the stack and standard array, for improved transport of insulin. The stack array generated a spatial peak temporal peak intensity (I(SPTP)) of 15.4 +/- 0.6 mW/cm(2) and the standard array had an I(SPTP) of 173.7 +/- 1.2 mW/cm(2). Spectrophotometeric absorption techniques were used for determining insulin transport in vitro across human skin. Compared with passive transmission (4.1 +/- 0.5 U) over an exposure period of 1 h, the standard array facilitated over a sevenfold increase in the noninvasive transdermal transport of Humulin R insulin (45.9 +/- 12.9 U). Using Humalog insulin with the standard array, there was a fourfold increase in the US-facilitated transmission over that in the control. These promising results indicate that low-frequency US can be used in a practical device for enhanced transport across the stratum corneum.

Administration, Cutaneous↗

PubMed2003

Ultrasound-mediated transdermal in vivo transport of insulin with low-profile cymbal arrays.

The purpose of this study was to demonstrate the feasibility of ultrasound (US)-mediated transdermal delivery of insulin in vivo using rats with a novel, low profile two-by-two US array based on the "cymbal" (due to its unique shape) transducer. As a practical device, the cymbal array (f = 20 kHz) was 37 x 37 x 7 mm in size, and weighed less than 22 g. A total of 20 Sprague-Dawley rats (350 to 450 g) were divided into four groups, two controls and two US exposure, with five rats in each group. The rats were anesthetized and shaved; a water-tight standoff reservoir, which held the insulin or saline, was sealed against the rat's abdomen and the US array. At the beginning of the experiment and every 30 min for 90 min, 0.3 mL of blood was collected from the jugular vein to determine the blood glucose level (mg/dL). For comparison between the rats, the change in the glucose level for each rat was normalized to a baseline (i.e., 0 mg/dL). The first control group used insulin in the reservoir with no US and the second control group had saline in the reservoir with US operating at I(SPTP) = 100 mW/cm(2) for 60 min. For the experiments, the third group employed insulin with US exposure for 60 min (I(SPTP) = 100 mW/cm(2)), whereas the last group used insulin with US operating with a 20-min exposure (I(SPTP) = 100 mW/cm(2)) to examine the effects of time on delivery. For the 60-min US exposure group, the glucose level was found to decrease from the baseline to -267.5 +/- 61.9 mg/dL in 1 h. Moreover, to study the effects of US exposure time on insulin delivery, the 20-min group had essentially the same result as the 60-min exposure at a similar intensity, which indicates that the expose time does not need to be as long for delivery.

Administration, Cutaneous↗

PubMed2002

Transducer design for a portable ultrasound enhanced transdermal drug-delivery system.

For application in a portable transdermal drug-delivery system, novel transducers have been designed to enhance insulin transmission across skin using ultrasound. Previous research has shown transdermal delivery of insulin across skin using commercial sonicators operating at 20 kHz with intensities ranging from 12.5 to 225 mW/cm2. The goal of this research was to design and construct a small, lightweight transducer or array that could operate with a similar frequency and intensity range as a commercial sonicator used in previous transdermal ultrasound insulin experiments, but without the weight and mass of a sonicator probe. To obtain this intensity range, a cymbal transducer design was chosen because of its light, compact structure and low resonance frequency in water. To increase the spatial ultrasound field for drug delivery across skin, two arrays, each comprising of four cymbal transducers, were constructed. The first array, designated the standard array, used four cymbals transducer elements in parallel. A second array (named the stack array) used four cymbal transducers that used stacked piezoelectric discs to drive the titanium flextensional caps. Under similar driving conditions, the standard array produced intensities comparable to those achieved using a commercial sonicator.

Administration, Cutaneous↗