Endoluminal high-intensity ultrasound offers spatially-precise thermal ablation of tissues adjacent to body lumens, but is constrained in treatment volume and penetration depth by the effective aperture of integrated transducers, which are limited in size to enable delivery through anatomical passages, endoscopic instrumentation, or laparoscopic ports. This study introduced and investigated three distinct endoluminal ultrasound applicator designs that can be delivered in a compact state then deployed or expanded at the target luminal site to increase the effective therapeutic aperture. The first design incorporated an array of planar transducers which could be unfolded at specific angles of convergence between the transducers. Two alternative designs consisted of fixed transducer sources surrounded by an expandable multicompartment balloon that contained acoustic reflector and dynamically-adjustable fluid lenses compartments. Parametric studies of acoustic output were performed across device design parameters via the rectangular radiator and secondary sources methods. Biothermal models were used to simulate resulting temperature distributions in three-dimensional heterogeneous tissue models. Simulations indicate that a deployable transducer array can increase volumetric coverage and penetration depth by ~80% and ~20%, respectively, while permitting more conformal thermal lesion shapes based on the degree of convergence between the transducers. The applicator designs incorporating reflector and fluid lenses demonstrated enhanced focal gain and penetration depth that increased with the diameter of the expanded reflector-lens balloon. Thermal simulations of assemblies with ~12 mm compact profiles and ~50 mm expanded balloon diameters demonstrated generation of localized thermal lesions at depths up to ~10 cm in liver tissue.
The speed of sound (SOS) for ultrasound devices used for imaging soft tissue is often calibrated to water, 1540 m/s1 , despite in-vivo soft tissue SOS varying from 1450 to 1613 m/s2 . Images acquired with 1540 m/s and used in conjunction with stereotactic external coordinate systems can thus result in displacement errors of several millimeters. Ultrasound imaging systems are routinely used to guide interventional thermal ablation and cryoablation devices, or radiation sources for brachytherapy3 . Brachytherapy uses small radioactive pellets, inserted interstitially with needles under ultrasound guidance, to eradicate cancerous tissue4 . Since the radiation dose diminishes with distance from the pellet as 1/r2 , imaging uncertainty of a few millimeters can result in significant erroneous dose delivery5,6. Likewise, modeling of power deposition and thermal dose accumulations from ablative sources are also prone to errors due to placement offsets from SOS errors7 . This work presents a method of mitigating needle placement error due to SOS variances without the need of ionizing radiation2,8. We demonstrate the effects of changes in dosimetry in a prostate brachytherapy environment due to patientspecific SOS variances and the ability to mitigate dose delivery uncertainty. Electromagnetic (EM) sensors embedded in the brachytherapy ultrasound system provide information regarding 3D position and orientation of the ultrasound array. Algorithms using data from these two modalities are used to correct bmode images to account for SOS errors. While ultrasound localization resulted in >3 mm displacements, EM resolution was verified to <1 mm precision using custom-built phantoms with various SOS, showing ~1% accuracy in SOS measurement.
KEYWORDS: Ultrasonography, In vivo imaging, Acoustics, Injuries, Buildings, In vitro testing, Systems modeling, Transducers, 3D acquisition, 3D metrology, Collagen, Proteins, Tissues, Surgery, Animal model studies
Discogenic back pain presents a major public health issue, with current therapeutic interventions limited to short-term symptom relief without providing regenerative remedies for diseased intervertebral discs (IVD). Many of these interventions are invasive and can diminish the biomechanical integrity of the IVDs. Low intensity pulsed ultrasound (LIPUS) is a potential treatment option that is both non-invasive and regenerative. LIPUS has been shown to be a clinically effective method for the enhancement of wound and fracture healing. Recent in vitro studies have shown that LIPUS stimulation induces an upregulation functional matrix proteins and downregulation of inflammatory factors in cultured IVD cells. However, we do not know the effects of LIPUS on an in vivo model for intervertebral disc degeneration. The objective of this study was to show technical feasibility of building a LIPUS system that can target the rat tail IVD and apply this setup to a model for acute IVD degeneration. A LIPUS exposimetry system was built using a 1.0 MHz planar transducer and custom housing. Ex vivo intensity measurements demonstrated LIPUS delivery to the center of the rat tail IVD. Using an established stab-incision model for disc degeneration, LIPUS was applied for 20 minutes daily for five days. For rats that displayed a significant injury response, LIPUS treatment caused significant upregulation of Collagen II and downregulation of Tumor Necrosis Factor – α gene expression. Our preliminary studies indicate technical feasibility of targeted delivery of ultrasound to a rat tail IVD for studies of LIPUS biological effects.
A treatment planning platform for interstitial microwave hyperthermia was developed for practical, free-hand clinical implants. Such implants, consisting of non-parallel, moderately curved antennas with varying insertion depths, are used in HDR brachytherapy for treating locally advanced cancer.
Numerical models for commercially available MA251 antennas (915 MHz, BSD Medical) were developed in COMSOL Multiphysics, a finite element analysis software package. To expedite treatment planning, electric fields, power deposition and temperature rises were computed for a single straight antenna in 2D axisymmetric geometry. A precomputed library of electric field and temperature solutions was created for a range of insertion depths (5-12 cm) and blood perfusion rates (0.5-5 kg/m3/s). 3D models of multiple antennas and benchtop phantoms experiments using temperature-sensitive liquid crystal paper to monitor heating by curved antennas were performed for comparative evaluation of the treatment planning platform.
A patient-customizable hyperthermia treatment planning software package was developed in MATLAB with capabilities to interface with a commercial radiation therapy planning platform (Oncentra, Nucleotron), import patient and multicatheter implant geometries, calculate insertion depths, and perform hyperthermia planning with antennas operating in asynchronous or synchronous mode. During asynchronous operation, the net power deposition and temperature rises were approximated as a superposition sum of the respective quantities for one single antenna. During synchronous excitation, a superposition of complex electrical fields was performed with appropriate phasing to compute power deposition. Electric fields and temperatures from the pre-computed single-antenna library were utilized following appropriate non-rigid coordinate transformations. Comparison to 3D models indicated that superposition of electric fields around parallel antennas is valid when they are at least 15 mm apart. Phantom experiments with curved antennas produced temperature profiles quite similar to those created using the planning system.
The hyperthermia planning software allowed users to select power and phasing, assess the corresponding 3D contours of energy and temperature, and optimize treatment parameters through gradient search techniques. The system produces fairly accurate temperature distributions in cases when the antennas are at least 15 mm apart.
The development and in vivo testing of a high-intensity ultrasound thermal ablation catheter for epicardial ablation of the left ventricle (LV) is presented. Scar tissue can occur in the mid-myocardial and epicardial space in patients with nonischemic cardiomyopathy and lead to ventricular tachycardia. Current ablation technology uses radiofrequency energy, which is limited epicardially by the presence of coronary vessels, phrenic nerves, and fat. Ultrasound energy can be precisely directed to deliver targeted deep epicardial ablation while sparing intervening epicardial nerve and vessels.
The proof-of-concept ultrasound applicators were designed for sub-xyphoid access to the pericardial space through a steerable 14-Fr sheath. The catheter consists of two rectangular planar transducers, for therapy (6.4 MHz) and imaging (5 MHz), mounted at the tip of a 3.5-mm flexible nylon catheter coupled and encapsulated within a custom-shaped balloon for cooling.
Thermal lesions were created in the LV in a swine (n = 10) model in vivo. The ultrasound applicator was positioned fluoroscopically. Its orientation and contact with the LV were verified using A-mode imaging and a radio-opaque marker. Ablations employed 60-s exposures at 15 – 30 W (electrical power). Histology indicated thermal coagulation and ablative lesions penetrating 8 – 12 mm into the left ventricle on lateral and anterior walls and along the left anterior descending artery.
The transducer design enabled successful sparing from the epicardial surface to 2 – 4 mm of intervening ventricle tissue and epicardial fat. The feasibility of targeted epicardial ablation with catheter-based ultrasound was demonstrated.
Real-time hyperpolarized (HP) 13C MR can be utilized during high-intensity focal ultrasound (HIFU) therapy to improve treatment delivery strategies, provide treatment verification, and thus reduce the need for more radical therapies for lowand intermediate-risk prostate cancers. The goal is to develop imaging biomarkers specific to thermal therapies of prostate cancer using HIFU, and to predict the success of thermal coagulation and identify tissues potentially sensitized to adjuvant treatment by sub-ablative hyperthermic heat doses. Mice with solid prostate tumors received HIFU treatment (5.6 MHz, 160W/cm2, 60 s), and the MR imaging follow-ups were performed on a wide-bore 14T microimaging system. 13C-labeled pyruvate and urea were used to monitor tumor metabolism and perfusion accordingly. After treatment, the ablated tumor tissue had a loss in metabolism and perfusion. In the regions receiving sub-ablative heat dose, a timedependent change in metabolism and perfusion was observed. The untreated regions behaved as a normal untreated TRAMP prostate tumor would. This promising preliminary study shows the potential of using 13C MR imaging as biomarkers of HIFU/thermal therapies.
An ultrasound applicator for endoluminal thermal therapy of pancreatic tumors has been introduced and evaluated through acoustic/biothermal simulations and ex vivo experimental investigations. Endoluminal therapeutic ultrasound constitutes a minimally invasive conformal therapy and is compatible with ultrasound or MR-based image guidance. The applicator would be placed in the stomach or duodenal lumen, and sonication would be performed through the luminal wall into the tumor, with concurrent water cooling of the wall tissue to prevent its thermal injury. A finite-element (FEM) 3D acoustic and biothermal model was implemented for theoretical analysis of the approach. Parametric studies over transducer geometries and frequencies revealed that operating frequencies within 1-3 MHz maximize penetration depth and lesion volume while sparing damage to the luminal wall. Patient-specific FEM models of pancreatic head tumors were generated and used to assess the feasibility of performing endoluminal ultrasound thermal ablation and hyperthermia of pancreatic tumors. Results indicated over 80% of the volume of small tumors (~2 cm diameter) within 35 mm of the duodenum could be safely ablated in under 30 minutes or elevated to hyperthermic temperatures at steady-state. Approximately 60% of a large tumor (~5 cm diameter) model could be safely ablated by considering multiple positions of the applicator along the length of the duodenum to increase coverage. Prototype applicators containing two 3.2 MHz planar transducers were fabricated and evaluated in ex vivo porcine carcass heating experiments under MR temperature imaging (MRTI) guidance. The applicator was positioned in the stomach adjacent to the pancreas, and sonications were performed for 10 min at 5 W/cm2 applied intensity. MRTI indicated over 400C temperature rise in pancreatic tissue with heating penetration extending 3 cm from the luminal wall.
Preferential heating of bone due to high ultrasound attenuation may enhance thermal ablation performed with cathetercooled
interstitial ultrasound applicators in or near bone. At the same time, thermally and acoustically insulating cortical
bone may protect sensitive structures nearby. 3D acoustic and biothermal transient finite element models were
developed to simulate temperature and thermal dose distributions during catheter-cooled interstitial ultrasound ablation
near bone. Experiments in ex vivo tissues and tissue-mimicking phantoms were performed to validate the models and to
quantify the temperature profiles and ablated volumes for various distances between the interstitial applicator and the
bone surface. 3D patient-specific models selected to bracket the range of clinical usage were developed to investigate
what types of tumors could be treated, applicator configurations, insertion paths, safety margins, and other parameters.
Experiments show that preferential heating at the bone surface decreases treatment times compared to when bone is
absent and that all tissue between an applicator and bone can be ablated when they are up to 2 cm apart. Simulations
indicate that a 5-7 mm safety margin of normal bone is needed to protect (thermal dose < 6 CEM43°C and T < 45°C) sensitive structures behind ablated bone. In 3D patient-specific simulations, tumors 1.0-3.8 cm (L) and 1.3-3.0 cm (D) near or within bone were ablated (thermal dose > 240 CEM43°C) within 10 min without damaging the nearby spinal cord, lungs, esophagus, trachea, or major vasculature. Preferential absorption of ultrasound by bone may provide
improved localization, faster treatment times, and larger treatment zones in tumors in and near bone compared to other
heating modalities.
Image-guided thermal interventions have been proposed for potential palliative and curative treatments of pancreatic
tumors. Catheter-based ultrasound devices offer the potential for temporal and 3D spatial control of the energy
deposition profile. The objective of this study was to apply theoretical and experimental techniques to investigate the
feasibility of endogastric, intraluminal and transgastric catheter-based ultrasound for MR guided thermal therapy of
pancreatic tumors. The transgastric approach involves insertion of a catheter-based ultrasound applicator (array of 1.5
mm OD x 10 mm transducers, 360° or sectored 180°, ~7 MHz frequency, 13-14G cooling catheter) directly into the
pancreas, either endoscopically or via image-guided percutaneous placement. An intraluminal applicator, of a more
flexible but similar construct, was considered for endoscopic insertion directly into the pancreatic or biliary duct. An
endoluminal approach was devised based on an ultrasound transducer assembly (tubular, planar, curvilinear) enclosed in
a cooling balloon which is endoscopically positioned within the stomach or duodenum, adjacent to pancreatic targets
from within the GI tract. A 3D acoustic bio-thermal model was implemented to calculate acoustic energy distributions
and used a FEM solver to determine the transient temperature and thermal dose profiles in tissue during heating. These
models were used to determine transducer parameters and delivery strategies and to study the feasibility of ablating 1-3
cm diameter tumors located 2-10 mm deep in the pancreas, while thermally sparing the stomach wall. Heterogeneous
acoustic and thermal properties were incorporated, including approximations for tumor desmoplasia and dynamic
changes during heating. A series of anatomic models based on imaging scans of representative patients were used to
investigate the three approaches. Proof of concept (POC) endogastric and transgastric applicators were fabricated and
experimentally evaluated in tissue mimicking phantoms, ex vivo tissue and in vivo canine model under multi-slice MR thermometry. RF micro-coils were evaluated to enable active catheter-tracking and prescription of thermometry slice
positions. Interstitial and intraluminal ultrasound applicators could be used to ablate (t43>240min) tumors measuring 2.3-3.4 cm in diameter when powered with 20-30 W/cm2 at 7 MHz for 5-10 min. Endoluminal applicators with planar and
curvilinear transducers operating at 3-4 MHz could be used to treat tumors up to 20-25 mm deep from the stomach wall
within 5 min. POC devices were fabricated and successfully integrated into the MRI environment with catheter tracking,
real-time thermometry and closed-loop feedback control.
Extensive surgical procedure or liver transplant still remains the gold standard for treating slow-growing tumors in liver.
But only few candidates are suitable for such procedure due to poor liver function, tumors in unresectable locations or presence of other liver diseases. In such situations, minimally invasive surgery may be the best therapeutic procedure. The use of RF, laser and ultrasound ablation techniques has gained considerable interest over the past several years to
treat liver diseases. The success of such minimally invasive procedure depends on accurately targeting the desired region
and guiding the entire procedure. The purpose of this study is to use ultrasound imaging and GPS tracking system to accurately place a steerable acoustic ablator and multiple temperature sensors in porcine liver in situ. Temperature
sensors were place at eight different locations to estimate thermal distribution in the three-dimensional treated volume.
Acoustic ablator of center frequency of 7 MHz was used for the experiments. During therapy a maximum temperature of
60-65 °C was observed at a distance 8-10 mm from the center of the ablation transducer. The dose distribution was
analyzed and compared with the gross pathology of the treated region. Accurate placement of the acoustic applicator and
temperature sensors were achieved using the combined image-guidance and the tracking system. By combining
ultrasound imaging and GPS tracking system accurate placement of catheter based acoustic ablation applicator can be achieved in livers in situ.
Catheter based ultrasound ablation devices have been suggested as the least minimally invasive procedure for thermal
therapy. The success of such procedures depends on accurately delivering the thermal dose to the tissue. One of the main
challenges of such therapy is to deliver thermal therapy at the target location without damaging the surrounding tissue or major vessels and veins. To achieve such multi-directional capability, a multi-angular beam pattern is required. The
purpose of this study was to build a multi-sectored tubular ultrasonic transducer and control the directionality of the
acoustic power delivered to the tissue by each sector simultaneously. Multi-zoned tubular ultrasonic transducer arrays
with three active sectors were constructed. Using these transducer configurations, a multi-angular ablation pattern was
created in ex vivo chicken breast tissue. Experiments were conducted by activating two and three zones separately to investigate the ablation pattern of each case. Simulations results were presented by solving the Penne bio-heat equation using finite element method. The simulation results were compared with ex vivo results with respect to temperature and dose distribution in the tissue. Thermocouples located at 15 mm radially from the applicator indicated a peak
temperature of greater than 52-55° C and thermal dose of 103-104 EQ mins at 43°C. It was observed through visual inspection that the proposed technology could ablate a specific tissue region or multiple regions selectively while not damaging the desired surrounding tissue. Good agreement between experimental and simulation results was obtained.
Feasibility of hyperthermia delivery to the prostate with a commercially available MR-guided endorectal ultrasound
(ERUS) phased array ablation system (ExAblate 2100, Insightec, LTD) was assessed through computer simulations and
ex vivo experiments.
The simulations included a 3D FEM-based biothermal model, and acoustic field calculations for the ExAblate phased
array (2.3 MHz, 2.3x4.0 cm2) using the rectangular radiator method. Array beamforming strategies were investigated to
deliver 30-min hyperthermia (<41 °C) to focal regions of prostate cancer, identified from MR images in representative
patient cases. Constraints on power densities, sonication durations and switching speeds imposed by ExAblate hardware
and software were incorporated in the models. T<41 °C was calculated in 14-19 cm3 for sonications with planar or
diverging beam patterns at 0.9-1.2 W/cm2, and in 3-10 cm3 for curvilinear (cylindrical) or multifocus beam patterns at
1.5-3.3 W/cm2, potentially useful for treating focal disease in a single posterior quadrant.
Preliminary experiments included beamformed sonications in tissue mimicking phantom material under MRI-based
temperature monitoring at 3T (GRE TE=7.0 ms, TR=15 ms, BW=10.5 kHz, FOV=15 cm, matrix 128x128, FA=40°).
MR-temperature rises of 2-6 °C were induced in a phantom with the ExAblate array, consistent with calculated values
and lower power settings (~0.86 W/cm2, 3 min.).
Conformable hyperthermia may be delivered by tailoring power deposition along the array length and angular expanse.
MRgERUS HIFU systems can be controlled for continuous hyperthermia in prostate to augment radiotherapy and drug
delivery. [FUS Foundation, NIH R01 122276, 111981].
Conformable hyperthermia can be administered in the prostate, immediately following radiation, using multiple (2-6)
directional ultrasound transducer arrays through previously implanted HDR brachytherapy catheters. These ultrasound
devices provided controlled heating in angle and length. To plan a hyperthermia treatment, the patient anatomy and
catheter geometry were reconstructed from CT images. Transducer powers were estimated to maximize the heated tumor
volume, while sparing the surrounding organs. Fast computation of temperature elevations was performed by
approximating the temperature rise induced at a point as the superposition of temperature increases resulting from
individual transducers. Steady state temperature increases due to individual transducer elements (90 - 360° sector angles,
0 - 2 W) were precalculated and stored in a lookup table. Instead of using computationally expensive 3D finite element
methods (FEM), temperature profiles were generated through interpolation and superposition of the precomputed data.
These approximate models were included in a gradient search optimization, reducing the treatment planning time by a
factor greater than 4.0 compared to the FE model. For 10 patient cases with dominant intraprostatic lesions, the
optimized treatment plans were furnished in 10 - 35 minutes and yielded T90 > 40.0°C in most cases. The corresponding
T90 values obtained through rigorous FE modeling were within 0.5 °C.
Radiofrequency (RF) ablation has emerged as an effective method for treating liver tumors under 3 cm in diameter.
Multiple applicator devices and techniques - using RF, microwave and other modalities - are under development for
thermal ablation of large and irregularly-shaped liver tumors. Interstitial ultrasound (IUS) applicators, comprised of
linear arrays of independently powered tubular transducers, enable 3D control of the spatial power deposition profile and
simultaneous ablation with multiple applicators. We evaluated IUS applicator configurations (parallel, converging and
diverging implants) suitable for percutaneous and laparascopic placement with experiments in ex vivo bovine tissue and
computational models. Ex vivo ablation zones measured 4.6±0.5 x 4.2±0.5 × 3.3±0.5 cm3 and 5.6±0.5 × 4.9±0.5 x
2.8±0.3 cm3 using three parallel applicators spaced 2 and 3 cm apart, respectively, and 4.0±0.3 × 3.2±0.4 × 2.9±0.2 cm3 using two parallel applicators spaced 2 cm apart. Computational models indicate in vivo ablation zones up to 4.5 × 4.4 × 5.5 cm3 and 5.7 × 4.8 × 5.2 cm3, using three applicators spaced 2 and 3 cm apart, respectively. Converging and diverging
implant patterns can also be employed for conformal ablation of irregularly-shaped tumor margins by tailoring power
levels along each device. Simultaneously powered interstitial ultrasound devices can create tailored ablation zones
comparable to currently available RF devices and similarly sized microwave antennas.
A clinical treatment delivery platform has been developed and is being evaluated in a clinical pilot study for providing
3D controlled hyperthermia with catheter-based ultrasound applicators in conjunction with high dose rate (HDR)
brachytherapy. Catheter-based ultrasound applicators are capable of 3D spatial control of heating in both angle and
length of the devices, with enhanced radial penetration of heating compared to other hyperthermia technologies.
Interstitial and endocavity ultrasound devices have been developed specifically for applying hyperthermia within HDR
brachytherapy implants during radiation therapy in the treatment of cervix and prostate. A pilot study of the
combination of catheter based ultrasound with HDR brachytherapy for locally advanced prostate and cervical cancer has
been initiated, and preliminary results of the performance and heating distributions are reported herein. The treatment
delivery platform consists of a 32 channel RF amplifier and a 48 channel thermocouple monitoring system. Controlling
software can monitor and regulate frequency and power to each transducer section as required during the procedure.
Interstitial applicators consist of multiple transducer sections of 2-4 cm length × 180 deg and 3-4 cm × 360 deg. heating
patterns to be inserted in specific placed 13g implant catheters. The endocavity device, designed to be inserted within a
6 mm OD plastic tandem catheter within the cervix, consists of 2-3 transducers × dual 180 or 360 deg sectors. 3D
temperature based treatment planning and optimization is dovetailed to the HDR optimization based planning to best
configure and position the applicators within the catheters, and to determine optimal base power levels to each
transducer section. To date we have treated eight cervix implants and six prostate implants. 100 % of treatments
achieved a goal of >60 min duration, with therapeutic temperatures achieved in all cases. Thermal dosimetry within the
hyperthermia target volume (HTV) and clinical target volume (CTV) are reported. Catheter-based ultrasound
hyperthermia with HDR appears feasible with therapeutic temperature coverage of the target volume within the prostate
or cervix while sparing surrounding more sensitive regions.
Ablation therapy is used as an alternative to surgical resection of hepatic tumors. In ablation, tumors are
destroyed through heating by RF current, high intensity focused ultrasound (HIFU), or other energy sources.
Ablation can be performed with a linear array transducer delivering unfocused intense ultrasound (<10
W/cm2). This allows simultaneous treatment and imaging, a feature uncommon in RF ablation. Unfocused
ultrasound can also enable faster bulk tissue ablation than HIFU.
In the experiments reported here, a 32-element linear array transducer with a 49 mm aperture delivers 3.1
MHz continuous wave unfocused ultrasound at amplitudes 0.7-1.4 MPa during the therapy cycle. It also
operates in pulse-echo mode to capture B-scan images. Ex-vivo fresh bovine liver tissue placed in degassed
saline is exposed to continuous wave ultrasound interleaved with brief pulsed ultrasound imaging cycles.
Tissue exposures range between 5 to 20 minutes. The following measurements are made at intervals of 1 to 3
seconds: tissue temperature with a needle thermocouple, acoustic emissions with a 1 MHz passive unfocused
detector, and tissue echogenicity from image brightness.
Passively detected acoustic emissions are used to quantify cavitation activity in the ablation experiments
presented here. As severity and extent of tissue ablation are related to temperature, this paper will statistically
model temperature as a function of tissue echogenicity and cavitation. The latter two quantities can
potentially be monitored noninvasively and used as a surrogate for temperature, enabling improved image
guidance and control of ultrasound ablation.
In North America, approximately 30,000 people annually suffer an aneurismal subarachnoid hemorrhage (SAH). Using computerized tomography (CT), the blood is generally not visible after 12 hours. Currently lumbar puncture (LP) results are equivocal for diagnosing SAH largely because of technical limitations in performing a quick and objective evaluation. Having ruptured once, an aneurysm is statistically more likely to rupture again. Therefore, for those individuals with a sentinel (or warning) hemorrhage, detection within the first 12 hours is paramount. We present a diagnostic technology based on visible spectroscopy to quickly and objectively assess low-blood volume SAH from a diagnostic spinal tap. This technology provides clinicians, with the resources necessary for assessing patients with suspected aneurismal SAH beyond the current 12-hour limitation imposed by CT scans. This aids in the improvement of patient care and results in rapid and appropriate treatment of the patient. To perform this diagnosis, we quantify bilirubin and hemoglobin in human CSF over a range of concentrations. Because the bilirubin and hemoglobin spectra overlap quantification is problematic. To solve this problem, two algorithmic approaches are presented: a statistical or a random stochastic component known as Partial Least Square (PLS) and a control theory based mathematical model. These algorithms account for the noise and distortion from blood in CSF leading to the quantification of bilirubin and methemoglobin spectroscopically. The configurations for a hardware platform is introduced, that is portable and user-friendly composed of specific components designed to have the sensitivity and specificity required. This aids in measuring bilirubin in CSF, hemorrhagic-CSF and CSF-like solutions. The prototype uses purpose built algorithms contained within the platform, such that physicians can use it in the hospital and lab as a point of care diagnostic test.
A weakened portion of an artery in the brain leads to a medical condition known as a cerebral aneurysm. A subarachnoid hemorrhage (SAH) occurs when an aneurysm ruptures. For those individuals suspected of having a SAH, a computerized tomography (CT) scan of the brain usually demonstrates evidence of the bleeding. However, in a considerable portion of people, the CT scan is unable to detect the blood that has escaped from the blood vessel. Recent studies have indicated nearly 30% of patients with a SAH are initially misdiagnosed. For circumstances when a SAH is suspected despite a normal CT scan, physicians make the diagnosis of SAH by performing a spinal tap. A spinal tap uses a needle to sample the cerebrospinal fluid (CSF) collected from the patient’s lumbar spine. However, it is also possible for blood to be introduced into the CSF as a result of the spinal tap procedure. Therefore, an effective solution is required to help medical personnel differentiate between the blood that results from a tap and that from a ruptured aneurysm. In this paper, the development of a prototype is described which is sensitive and specific for measuring bilirubin in CSF, hemorrhagic-CSF and CSF-like solutions. To develop this instrument a combination of spectrophotometric analysis, custom data analysis software and other hardware interfaces are assembled that lay the foundation for the development of portable and user-friendly equipment suitable for assisting trained medical personnel with the diagnosis of a ruptured cerebral aneurysm.
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