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ABSTRACT: Abstract Purpose: A generalised polynomial chaos (gPC) method is used to incorporate constitutive parameter uncertainties within the Pennes representation of bioheat transfer phenomena. The stochastic temperature predictions of the mathematical model are critically evaluated against MR thermometry data for planning MR-guided laser-induced thermal therapies (MRgLITT). Methods: The Pennes bioheat transfer model coupled with a diffusion theory approximation of laser tissue interaction was implemented as the underlying deterministic kernel. A probabilistic sensitivity study was used to identify parameters that provide the most variance in temperature output. Confidence intervals of the temperature predictions are compared to MR temperature imaging (MRTI) obtained during phantom and in vivo canine (n = 4) MRgLITT experiments. The gPC predictions were quantitatively compared to MRTI data using probabilistic linear and temporal profiles as well as 2-D 60 °C isotherms. Results: Optical parameters provided the highest variance in the model output (peak standard deviation: anisotropy 3.51 °C, absorption 2.94 °C, scattering 1.84 °C, conductivity 1.43 °C, and perfusion 0.94 °C). Further, within the statistical sense considered, a non-linear model of the temperature and damage-dependent perfusion, absorption, and scattering is captured within the confidence intervals of the linear gPC method. Multivariate stochastic model predictions using parameters with the dominant sensitivities show good agreement with experimental MRTI data. Conclusions: Given parameter uncertainties and mathematical modelling approximations of the Pennes bioheat model, the statistical framework demonstrates conservative estimates of the therapeutic heating and has potential for use as a computational prediction tool for thermal therapy planning.
International Journal of Hyperthermia 05/2013; · 1.92 Impact Factor
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ABSTRACT: OBJECTIVES: Real-time magnetic resonance imaging (MRI)-guided cryoablation has been investigated in open MRI systems with low magnetic fields (0.2-0.5 T). More advanced imaging techniques and faster imaging rates are possible at higher magnetic fields, which often require a closed-bore magnet design. However, there is very little experience with real-time interventions in closed-bore 1.5-T MRI units. Herein, we report our initial experience with real-time MRI-guided cryoablation of small renal tumors using a prototype balanced steady-state free precession imaging sequence in a closed-bore 1.5-T MRI system. MATERIALS AND METHODS: From August 2008 to April 2012, 18 patients underwent MRI-guided cryoablation of small renal tumors. A 1.5-T cylindrical MRI scanner with a 125 cm × 70 cm bore and a prototype balanced steady-state free precession sequence (BEAT interactive real-time tip tracking) were used to guide the placement of 17-gauge cryoprobes in real time. Ice ball formation was monitored every 3 minutes in 1 or more imaging planes. Each ablation consisted of 2 freeze-thaw cycles. Contrast-enhanced MRI was performed after the second active thaw period. Follow-up consisted of clinical evaluation and renal protocol computed tomography (CT) or MRI performed at 1, 6, 12, 18, and 24 months and annually thereafter. RESULTS: During the study period, we successfully ablated 18 tumors in 18 patients in 18 sessions. The mean tumor size was 2.2 cm (median, 2 cm; range, 1.2-4.4 cm). The number of cryoprobes used per patient was determined based on tumor size. The mean number of cryoprobes used per patient was 3 (median, 3 cryoprobes; range, 2-4 cryoprobes). Fifty-six cryoprobes, 9 biopsy needles, and 2 hydrodissection needles were successfully placed under real-time MRI guidance using BEAT interactive real-time tip tracking sequence. Hydrodissection under MRI guidance was successfully performed in 4 patients. In each patient, contrast-enhanced MRI performed after the second active thaw period revealed a sharply defined avascular zone surrounding the targeted tumor, which confirmed complete ablation of the tumor with adequate margins. Although contrast media slowly accumulated in the targeted tumor in 9 patients immediately after the procedure, follow-up imaging studies performed at a mean of 16.7 months revealed no contrast enhancement within the ablation zone in these patients. Disease-specific, metastasis-free, and local recurrence-free survival rates were all 100%. CONCLUSIONS: Real-time placement and manipulation of cryoprobes during MRI-guided cryoablation of small renal tumors in a closed-bore, high-magnetic field scanner are feasible. Technical and clinical success rates are similar to those of patients who undergo CT-guided radiofrequency ablation or cryoablation of small renal tumors. Our findings suggest that MRI-guided ablation has several advantages over CT-guided ablation, including real-time guidance for probe placement, multiplanar imaging, exquisite soft tissue contrast, and lack of ionizing radiation.
Investigative radiology 03/2013; · 4.85 Impact Factor
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ABSTRACT: Advances in nanotechnology for oncology will arise from an increased understanding of the interaction between nanomaterials and biological systems; refinement of multifunctional nanocomposites for applications such as simultaneous imaging and therapy (theranostics); and harnessing of the unique physicochemical properties arising from nanoscale effects which distinguish them from small-molecular-weight molecules in the detection and destruction of cancer cells with high selectivity and efficiency. The major challenges in successful clinical translation of tumor specific nanoparticle delivery include overcoming various biological barriers and demonstrating enhanced therapeutic efficacy over the current standard of care in the clinic. For many nanoparticle mediated theranostic applications, image guidance can play a crucial role not only in exploiting the cancer specific imaging capabilities of these novel particles, but in planning, targeting, monitoring and verifying treatment delivery, thus enhancing the safety and efficacy of these emerging procedures.
Journal of Controlled Release 08/2012; · 5.73 Impact Factor
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Sanjay Gupta, R Jason Stafford,
Sanaz Javadi,
Efe Ozkan,
Joe E Ensor,
Kenneth C Wright,
Andrew M Elliot,
You Jian,
Rita E Serda,
Katherine A Dixon,
Jennifer J Miller,
Sherry Klump,
Michael J Wallace,
Chun Li
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ABSTRACT: To evaluate the effects of near-infrared (NIR) laser irradiation of microspheres (MS) containing hollow gold nanospheres (HAuNS) and paclitaxel (PTX) administered intraarterially in an animal model.
For the ex vivo experiments, VX2 tumor-bearing rabbits underwent administration of MS-HAuNS or MS via the hepatic artery (HA). The animals were killed, the liver tumors were subjected to NIR irradiation, and temperature changes were estimated with magnetic resonance (MR) imaging. For the in vivo study, VX2 tumor-bearing rabbits were randomly assigned to three groups: MS-HAuNS-PTX-plus-NIR, MS-HAuNS-PTX, and saline-plus-NIR. Laser irradiation was delivered at 1 hour and at 3 days after administration of saline or MS-HAuNS-PTX via the HA. Animals were euthanized, and tumors were analyzed for necrosis and apoptosis. Plasma samples were collected from the MS-HAuNS-PTX-plus-NIR animals for PTX analysis.
Ex vivo experiments showed intratumoral heating in animals that received MS-HAuNS but no temperature change in animals that received MS. Animals treated with MS-HAuNS-PTX-plus-NIR showed a transient increase in plasma PTX levels after each NIR irradiation and significantly greater tumor necrosis than animals that received MS-HAuNS-PTX or saline-plus-NIR (44.9% vs 13.8% or 23.7%; P < .0001). The mean apoptotic index in the MS-HAuNS-PTX-plus-NIR group (5.01 ± 1.66) was significantly higher than the mean apoptotic index in the MS-HAuNS-PTX (2.99 ± 0.97) or saline-plus-NIR (1.96 ± 0.40) groups (P = .0013).
NIR laser irradiation after MS-HAuNS-PTX administration results in intratumoral heating and increases the efficacy of treatment. Further studies are required to evaluate the optimal laser settings to maximize therapeutic efficacy.
Journal of vascular and interventional radiology: JVIR 02/2012; 23(4):553-61. · 1.81 Impact Factor
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ABSTRACT: We report the final results of a pilot clinical trial exploring the safety and feasibility of real-time magnetic resonance-guided laser-induced thermal therapy (MRgLITT) for treatment of resistant focal metastatic intracranial tumors.
In patients with chemotherapy, whole-brain radiation, and radiosurgery resistant metastatic intracranial tumors, minimally invasive stereotaxic placement of a saline-cooled interstitial fiberoptic laser applicator under local anesthesia was followed by laser irradiation during continuous magnetic resonance imaging (MRI) scanning. A computer workstation extracted real-time temperature-sensitive information for feedback control over laser delivery. A total of 15 metastatic tumors were treated in 7 patients. Patients were followed with physical exam and imaging for 30 months.
In all cases, the procedure was well tolerated, and patients were discharged home within 24 hours. Follow-up imaging at up to 30 months showed an acute increase in apparent lesion volume followed by a gradual and steady decrease. No tumor recurrence within thermal ablation zones was noted. Kaplan-Meier analysis indicated that the median survival was 19.8 months.
Real-time magnetic resonance (MR) guidance of laser-induced thermal therapy (LITT) offers a high level of control. This tool therefore enables a minimally invasive option for destruction and treatment of resistant focal metastatic intracranial tumors. MR-guided LITT appears to provide a safe and potentially effective treatment for recurrent focal metastatic brain disease. A larger phase II and III series would be of interest to quantify potential median survival advantage.
Lasers in Surgery and Medicine 11/2011; 43(10):943-50. · 2.75 Impact Factor
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ABSTRACT: Image-guided thermal ablation of tumors is becoming a more widely accepted minimally invasive alternative to surgery for patients who are not good surgical candidates, such as patients with advanced head and neck cancer. In this study, multifunctional superparamagnetic iron oxide coated with gold nanoshell (SPIO@Au NS) that have both optical and magnetic properties was conjugated with the targeting agent, C225 monoclonal antibody, against epidermal growth factor receptor (EGFR). C225-SPIO@Au NS have an average a diameter of 82 ± 4.4 nm, contain 142 ± 15 antibodies per nanoshell, have an absorption peak in the near infrared (~800 nm), and have transverse relaxivity (r(2)) of 193 and 353 mM(-1) s(-1) versus Feridex™ of 171 and 300 mM(-1) s(-1), using 1.5 T and 7 T MR scanners, respectively. Specific targeting of the synthesized C225-SPIO@Au NS was tested in vitro using A431 cells and oral cancer cells, FaDu, OSC19, and HN5, all of which overexpress EGFR. Selective binding was achieved using C225-SPIO@Au NS but not with the non-targeting PEG-SPIO@Au NS and blocking group (excess of C225 + C225-SPIO@Au NS). In vivo biodistribution on mice bearing A431 tumors also showed selective targeting of C225-SPIO@Au NS compared with the non-targeting and blocking groups. The selective photothermal ablation of the nanoshells shows that without laser treatment there were no cell death and among the groups that were treated with laser at a power of 36 W/cm(2) for 3 min, only the cells treated with C225-SPIO@Au NS had cell killing (p < 0.001). In summary, successful synthesis and characterization of targeted C225-SPIO@Au NS demonstrating both superparamagnetic and optical properties has been achieved. We have shown both in vitro and in vivo that these nanoshells are MR-active and can be selectively heated up for simultaneous imaging and photothermal ablation therapy.
Biomaterials 10/2011; 32(30):7600-8. · 7.40 Impact Factor
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ABSTRACT: Image-guided thermal ablation of bone tumors is gaining acceptance in the oncology community. Computed tomography-guided radiofrequency ablation and cryoablation are widely available and are used in clinical practice. However, a potentially devastating complication of these techniques is thermal injury to the spinal cord and nerve roots in patients with tumors involving the vertebra, paraspinal tissues, or pelvis. Magnetic resonance imaging-guided laser ablation with quantitative magnetic resonance temperature imaging is a novel technique that allows for accurate imaging of the tumor, real-time placement of laser fibers, and real-time monitoring of the ablation zone. With this technique, target temperature thresholds are placed on critical neural elements to provide real-time feedback that allows for automatic deactivation of the laser when the threshold temperature is reached. The ablation zone is generated quickly, with sharp and well-demarcated boundaries. As such, magnetic resonance imaging-guided laser ablation may be a safer technique for ablating bone tumors in the vicinity of the spinal cord, nerve roots, and peripheral nerves.
Techniques in vascular and interventional radiology 09/2011; 14(3):177-82.
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Wei Lu,
Marites P Melancon,
Chiyi Xiong,
Qian Huang,
Andrew Elliott,
Shaoli Song,
Rui Zhang,
Leo G Flores,
Juri G Gelovani,
Lihong V Wang,
Geng Ku, R Jason Stafford,
Chun Li
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ABSTRACT: Advancements in nanotechnology have made it possible to create multifunctional nanostructures that can be used simultaneously to image and treat cancers. For example, hollow gold nanospheres (HAuNS) have been shown to generate intense photoacoustic signals and induce efficient photothermal ablation (PTA) therapy. In this study, we used photoacoustic tomography, a hybrid imaging modality, to assess the intravenous delivery of HAuNS targeted to integrins that are overexpressed in both glioma and angiogenic blood vessels in a mouse model of glioma. Mice were then treated with near-infrared laser, which elevated tumor temperature by 20.7°C. We found that PTA treatment significantly prolonged the survival of tumor-bearing mice. Taken together, these results show the feasibility of using a single nanostructure for image-guided local tumor PTA therapy with photoacoustic molecular imaging.
Cancer Research 08/2011; 71(19):6116-21. · 7.86 Impact Factor
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ABSTRACT: The objective of this study was to report a single-center experience with magnetic resonance imaging (MRI)-guided biopsy in the musculoskeletal system using a closed-bore, cylindrical, high-magnetic-field (1.5-T) MRI unit.
From May 2010 to July 2011, 100 consecutive MRI-guided biopsy sessions were undertaken for musculoskeletal lesions in 97 patients. Patient demographics, tumor characteristics, and biopsy techniques were recorded. Biopsy results, treatment outcomes, and follow-up imaging studies were reviewed.
Biopsy procedures were technically successful in 99 cases (99%). Despite a mean body mass index of 30 kg/m, all patients fit within the bore of the magnet. There were 69 soft-tissue and 31 bone tumors. Most patients had both tissue core (n = 93) and fine-needle aspiration (n = 84) biopsies. All lesions were adequately imaged, localized, and targeted using rapid balanced steady-state free precession imaging (89%), fast T1 (4%), or combination of the 2 techniques (7%). A prototype real-time imaging sequence was used in 29 cases (29%) to guide biopsy needle insertion. There were no major complications. Sensitivity, specificity, and overall accuracy were 97%, 100%, and 97.6%, respectively.
Magnetic resonance imaging-guided biopsy in a closed-bore, high-field-strength magnet is a safe, easy, and effective technique for evaluation of musculoskeletal lesions. Ideally, the MRI suite should be equipped with an in-room radiofrequency-shielded monitor and a communication system. However, surface coils with adequate opening to grant access to the biopsy site, MRI-compatible needles, and MRI-compatible patient monitoring devices are absolutely necessary to perform MRI-guided biopsies.
Topics in magnetic resonance imaging: TMRI 08/2011; 22(4):189-96.
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ABSTRACT: Hyperthermia, which is heating of tumors above 43°C for about 30min, has been known to modulate vascular permeability for enhanced chemotherapy. However, it is not clear whether a similar effect exists when temperature at tumor sites is elevated above 43°C, such as temperature achieved in laser-induced photothermal ablation (PTA) therapy. Also, the effect of timing of chemotherapeutic drug administration following heating in the efficiency of drug delivery is not established. In this study, we investigated the impact of near infrared (NIR) laser irradiated anti-EGFR monoclonal antibody C225-conjugated hollow gold nanospheres (C225-HAuNS) on vascular permeability and subsequent tumor uptake of a water-soluble polymer using combined MRI, ultrasound and optical imaging approaches. Magnetic temperature imaging showed a maximum temperature of 65.2±0.10 °C in A431 tumor xenograft of mice treated with C225-HAuNS plus laser and 47.0±0.33 °C in tumors of mice treated with saline plus laser at 4 W/cm² for 3 min (control) at 2 mm from the light incident surface. Dynamic contrast enhanced (DCE) MRI demonstrated greater than 2-fold increase of DTPA-Gd in the initial area under the curve (IAUC₉₀) in mice injected with C225-HAuNS and exposed to NIR laser compared with control mice at 3 min after laser treatment. Similarly, Power Doppler (PD) ultrasound revealed a 4- to 6-fold increase in percentage vascularization in mice treated with C225-HAuNS plus NIR laser compared to control mice and confirmed increased vascular perfusion immediately after laser treatment. Twenty-four hours later, the blood perfusion was shut down. On optical imaging, tumor uptake of PG-Gd-NIR813, which is the model polymeric drug used, was significantly higher (p-value<0.05) in mice injected with PG-Gd-NIR813 at 5 min after laser treatment than in mice injected with PG-Gd-NIR813 at 24h after laser treatment and the saline-treated mice. In conclusion, laser irradiation of tumors after intravenous injection of C255-HAuNS induces a thermally mediated modulation of the vascular perfusion, which enhances the delivery of polymeric drugs to the tumors at the time phototherapy is initiated.
Journal of Controlled Release 07/2011; 156(2):265-72. · 5.73 Impact Factor
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ABSTRACT: To provide quantitative temperature monitoring for thermal therapies in bone marrow by measuring temperature-dependent signal changes in the bone marrow of ex vivo canine femurs heated with a 980-nm laser at 1.5T and 3.0T.
Using a multi-gradient echo (≤ 16) acquisition and signal modeling with the Stieglitz-McBride algorithm, the temperature sensitivity coefficients (TSC, ppm/°C) of water and multiple lipid components' proton resonance frequency (PRF) values are measured at high spatiotemporal resolutions (1.6 × 1.6 × 4 mm(3) , ≤ 5 seconds). Responses in R(2) * and amplitudes of each peak were also measured as a function of temperature simultaneously.
Calibrations demonstrate that lipid signal may be used to compensate for B(0) errors to provide accurate temperature readings (<1.0°C). Over a temperature range of 17.2-57.2°C, the TSCs after correction to a bulk methylene reference are -0.87 × 10(-2) ± 4.7 × 10(-4) ppm/°C and -0.87 × 10(-2) ± 4.0 × 10(-4) ppm/°C for 1.5T and 3.0T, respectively.
Overall, we demonstrate that accurate and precise temperature measurements can be made in bone marrow. In addition, the relationship of R(2) * and signal amplitudes with respect to temperature are shown to differ significantly where conformal changes are predicted by Arrhenius rate model analysis.
Journal of Magnetic Resonance Imaging 05/2011; 33(5):1128-35. · 2.70 Impact Factor
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ABSTRACT: To evaluate the effect of half-dose intravenous gadolinium contrast on the enhancement of bone and soft tissue tumors.
This study is HIPAA compliant and informed consent was waived by the institutional review board. An institutional database search was performed over a 1-year period for patients with full- and half-dose MR examinations performed for musculoskeletal oncologic indications. Examination pairs that were identical with regard to field strength and presence or absence of fat saturation were included, resulting in 29 paired examinations. When multiple, the lesion that was best delineated and enhanced well on the first examination in the pair was chosen, yielding 17 bone and 12 soft tissue. Five musculoskeletal radiologists blinded to dosages were asked to assess for a difference in enhancement when comparing the lesion on both examinations and to rate the degree of difference on a three-point scale. They were also asked to identify the examination on which the lesion enhanced less (tallied as low dose). Results were analyzed with the exact binomial test.
The readers perceived an enhancement difference in 41% (59/145) of studies (p = 0.03) and the majority were rated as "mild" (66%, 39/59). The readers did not accurately identify the low-dose examinations (54% correctly identified, 32/59, p = 0.60).
Half-dose gadolinium enhancement of lesions could not be accurately distinguished from full-dose enhancement upon review of the same lesion imaged at both concentrations.
Skeletal Radiology 03/2011; 40(3):327-33. · 1.54 Impact Factor
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ABSTRACT: Proton resonance frequency shift thermometry is sensitive to breathing motion that leads to incorrect phase differences. In this work, a novel velocity-sensitive navigator technique for triggering MR thermometry image acquisition is presented.
A segmented echo planar imaging pulse sequence was modified for velocity-triggered temperature mapping. Trigger events were generated when the estimated velocity value was less than 0.2 cm/s during the slowdown phase in parallel to the velocity-encoding direction. To remove remaining high-frequency spikes from pulsation in real time, a Kalman filter was applied to the velocity navigator data. A phantom experiment with heating and an initial volunteer experiment without heating were performed to show the applicability of this technique. Additionally, a breath-hold experiment was conducted for comparison.
A temperature rise of ΔT = +37.3°C was seen in the phantom experiment, and a root mean square error (RMSE) outside the heated region of 2.3°C could be obtained for periodic motion. In the volunteer experiment, a RMSE of 2.7°C/2.9°C (triggered vs. breath hold) was measured.
A novel velocity navigator with Kalman filter postprocessing in real time significantly improves the temperature accuracy over non-triggered acquisitions and suggests being comparable to a breath-held acquisition. The proposed technique might be clinically applied for monitoring of thermal ablations in abdominal organs.
MAGMA Magnetic Resonance Materials in Physics Biology and Medicine 03/2011; 25(1):15-22. · 1.88 Impact Factor
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ABSTRACT: to investigate the multifunctional imaging and therapeutic capabilities of core-shell nanoparticles composed of a superparamagnetic iron oxide (SPIO) core and a gold shell (SPIO@AuNS).
the magnetic/optical properties of SPIO@AuNS were examined both in an agar gel phantom and in vivo by evaluating contrast-enhanced magnetic resonance imaging (MRI) and by measuring near-infrared (NIR) light-induced temperature changes mediated by SPIO@AuNS. In addition, the biodistribution and pharmacokinetics of In-labeled SPIO@AuNS after intravenous injection in mice bearing A431 tumors were evaluated in the presence and absence of an external magnet.
: In agar phantoms containing SPIO@AuNS, a significant contrast enhancement in T2-weighted MRI was observed and a linear increase in temperature was observed with increasing concentration and laser output power when irradiated with NIR light centered at an 808 nm. In vivo, T2*-MRI delineated SPIO@AuNS and magnetic resonance temperature imaging of the same tumors revealed significant temperature elevations when intratumorally injected with SPIO@AuNS (1 × 10 particles/mouse) and irradiated with NIR light (65.70°C ± 0.69°C vs. 44.23°C ± 0.24°C for saline + laser). Biodistribution studies in mice intravenously injected with In-labeled-SPIO@AuNS(1 × 10 particles/mouse) had an approximately 2-fold increase in SPIO@AuNS delivered into tumors in the presence of an external magnet compared with tumors without the magnet.
owing to its ability to mediate efficient photothermal ablation of cancer cells under MRI guidance, as well as the ability to be directed to solid tumors with an external magnetic field gradient, multifunctional SPIO@AuNS is a promising theranostic nanoplatform.
Investigative radiology 02/2011; 46(2):132-40. · 4.85 Impact Factor
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Steven J Frank,
Ramesh C Tailor,
Rajat J Kudchadker,
Karen S Martirosyan, R Jason Stafford,
Andrew M Elliott,
David A Swanson,
David Sing,
Jonathan Choi,
Firas Mourtada,
Geoffrey S Ibbott
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ABSTRACT: We have developed a novel MRI marker for prostate brachytherapy. The purpose of this study was to evaluate the changes in anisotropy when cobalt chloride complex contrast agent encapsulated contrast agent markers (C4-ECAM) were placed adjacent to an iodine-125 (I-125) titanium seed, and to verify that the C4-ECAMs were visible on magnetic resonance imaging (MRI) after radiation exposure. Two C4-ECAMs were verified to be MRI visible in a phantom before radiation exposure. The C4-ECAMs were then attached to each end of a 12.7-U (10-mCi) I-125 titanium seed in a polymer tube. Anisotropy was measured and analyzed with the seed alone and with attached C4-ECAMs by suspending thermoluminescent dosimeters in a water phantom in 2 circles surrounding the radioactive source with radius of 1 or 2 cm. A T1-weighted MRI evaluation of C4-ECAMs was then performed after exposure to the amount of radiation typically delivered during 1 month of prostate brachytherapy. Measured values of the anisotropy function F(r, θ) for the I-125 seed with and without the C4-ECAMs were mutually statistically indistinguishable (standard error of the mean <4.2%) and agreed well with published TG-43 values for the bare seed. As expected, the anisotropy function ϕ(an)(r) for the 2 datasets (with and without C4-ECAMs) derived from the measured F(r, θ) did not exhibit statistically measurable difference. Both datasets showed agreement with the published TG-43 ϕ(an)(r) for the bare seed. The C4-ECAMs were well visualized by MRI after 1 month of radiation exposure. There were no changes in anisotropy when the C4-ECAMs were placed next to an I-125 radioactive seed, and the C4-ECAMs were visualized after radiation exposure.
Medical dosimetry: official journal of the American Association of Medical Dosimetrists 01/2011; 36(2):200-5. · 1.26 Impact Factor
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ABSTRACT: Minimally invasive thermal therapy using high-power diode lasers is an active area of clinical research. Gold nanoshells (AuNS) can be tuned to absorb light in the range used for laser ablation and may facilitate more conformal tumor heating and sparing of normal tissue via enhanced tumor specific heating. This concept was investigated in a xenograft model of prostate cancer (PC-3) using MR temperature imaging (MRTI) in a 1.5T scanner to characterize the spatiotemporal temperature distribution resulting from nanoparticle mediated heating. Tumors with and without intravenously injected AuNS were exposed to an external laser tuned to 808 nm for 180 sec at 4 W/cm(2) under real-time monitoring with proton resonance frequency shift based MRTI. Microscopy indicated that these nanoparticles (140-150 nm) accumulated passively in the tumor and remained close to the tumor microvasculature. MRTI measured a statistically significant (p < 0.001) increase in maximum temperature in the tumor cortex (mean = 21 ± 7°C) in +AuNS tumors versus control tumors. Analysis of the temperature maps helped demonstrate that the overall distribution of temperature within +AuNS tumors was demonstrably higher versus control, and resulted in damage visible on histopathology. This research demonstrates that passive uptake of intravenously injected AuNS in PC-3 xenografts converts the tumor vasculature into a potent heating source for nanoparticle mediated ablation at power levels which do not generate significant damage in normal tissue. When used in conjunction with MRTI, this has implications for development and validation of more conformal delivery of therapy for interstitial laser ablations.
International Journal of Hyperthermia 01/2011; 27(8):782-90. · 1.92 Impact Factor
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ABSTRACT: Sub-lethal temperature elevations in the tumour incurred during laser cancer therapy can induce heat shock protein (HSP) expression leading to enhanced tumour survival and recurrence. Nanoshells utilised in combination with laser therapy can potentially enable selective heat deposition, greater thermal injury, and diminished HSP expression in the tumour. The study objective was to measure the distribution of temperature and HSP expression in prostate tumours in response to laser therapy alone or with nanoshells to determine if these combinatorial therapies can minimise HSP expression.
PC3 cells were inoculated in the backs of CB17-Prkd c SCID/J mice and treated with external laser irradiation (wavelength of 810 nm, irradiance of 5 W/cm(2), spot size of 5 mm, and heating duration of 3 min) alone or in combination with gold nanoshells (diameter of 55 nm and outer gold shell thickness of 10 nm) introduced into the tumour 24 h prior to laser treatment. Magnetic resonance temperature imaging was used to measure the distribution of temperature elevation in the tumours during laser treatment. Tumours were sectioned 16 h following laser treatment, stained for Hsp27 and Hsp70, imaged with a confocal microscope, and HSP expression levels were quantified as a function of depth in the tumours.
Maximum temperature elevations at the tumour surface were 28°C for laser treatment only and 50°C for laser heating in combination with gold nanoshells. Laser therapy alone caused significant induction of HSP expression in the first few millimeters of the tumour depth, whereas decreasing HSP expression occurred with greater tumour depth. Tumours treated with laser and nanoshells experienced substantial temperatures (73-78°C) at the tumour surface and temperatures greater than 53°C in the first few millimeters which eliminated HSP expression.
Inclusion of nanoshells in laser therapy can provide a mechanism for enhancing heat deposition capable of eliminating HSP expression within a larger tumour region compared to laser heating alone.
International Journal of Hyperthermia 01/2011; 27(8):791-801. · 1.92 Impact Factor
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ABSTRACT: We evaluated a newly Food and Drug Administration cleared, closed loop, magnetic resonance guided laser induced interstitial thermal therapy system for targeted ablation of prostate tissue to assess the feasibility of targeting, real-time monitoring and predicting lesion generation in the magnetic resonance environment.
Seven mongrel dogs (University of Texas Health Science Center, Houston, Texas) with (2) and without (5) canine transmissible venereal tumors in the prostate were imaged with a 1.5 T magnetic resonance imaging scanner. Real-time 3-dimensional magnetic resonance imaging was used to accurately position water cooled, 980 nm laser applicators to predetermined targets in the canine prostate. Destruction of targeted tissue was guided by real-time magnetic resonance temperature imaging to precisely control thermal ablation. Magnetic resonance predictions of thermal damage were correlated with posttreatment imaging results and compared to histopathology findings.
Template based targeting using magnetic resonance guidance allowed the laser applicator to be placed within a mean ± SD of 1.1 ± 0.7 mm of the target site. Mean width and length of the ablation zone on magnetic resonance imaging were 13.7 ± 1.3 and 19.0 ± 4.2 mm, respectively, using single and compound exposures. The damage predicted by magnetic resonance based thermal damage calculations correlated with the damage on posttreatment imaging with a slope near unity and excellent correlation (r(2) = 0.94).
This laser induced interstitial thermal therapy system provided rapid, localized tissue heating under magnetic resonance temperature imaging control. Combined with real-time monitoring and template based planning, magnetic resonance guided, laser induced interstitial thermal therapy is an attractive modality for prostate cancer focal therapy.
The Journal of urology 10/2010; 184(4):1514-20. · 4.02 Impact Factor
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ABSTRACT: To evaluate the accuracy of computer simulation in predicting the thermal damage region produced by a radiofrequency (RF) ablation procedure in an in vitro perfused bovine liver model. The thermal dose end point in the liver model is used to assess quantitatively computer prediction for use in prospective treatment planning of RF ablation procedures.
Geometric details of the tri-cooled tip electrode were modeled. The resistive heating of a pulsed voltage delivery was simulated in four dimensions using finite element models (FEM) implemented on high-performance parallel computing architectures. A range of physically realistic blood perfusion parameters, 3.6-53.6 kg/sec/m(3), was considered in the computer model. An Arrhenius damage model was used to predict the thermal dose. Dice similarity coefficients (DSC) were the metric of comparison between computational predictions and T1-weighted contrast-enhanced images of the damage obtained from a RF procedure performed on an in vitro perfused bovine liver model.
For a perfusion parameter greater than 16.3 kg/sec/m(3), simulations predict the temporal evolution of the damaged volume is perfusion limited and will reach a maximum value. Over a range of physically meaningful perfusion values, 16.3-33.1 kg/sec/m(3), the predicted thermal dose reaches the maximum damage volume within 2 minutes of the delivery and is in good agreement (DSC > 0.7) with experimental measurements obtained from the perfused liver model.
As measured by the computed volumetric DSC, computer prediction accuracy of the thermal dose shows good correlation with ablation lesions measured in vitro in perfused bovine liver models over a range of physically realistic perfusion values.
Journal of vascular and interventional radiology: JVIR 10/2010; 21(11):1725-32. · 1.81 Impact Factor
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ABSTRACT: Minimally invasive thermal ablative therapies as alternatives to conventional surgical management of solid tumors and other pathologies is increasing owing to the potential benefits of performing these procedures in an outpatient setting with reduced complications and comorbidity. Magnetic resonance temperature imaging (MRTI) measurement allows existing thermal dose models to use the spatiotemporal temperature history to estimate the thermal damage to tissue. However, the various thermal dose models presented in the literature employ different parameters and thresholds, affecting the reliability of thermal dosimetry. In this study, the authors quantitatively compared three thermal dose models (Arrhenius rate process, CEM43, and threshold temperature) using the dice similarity coefficient (DSC).
The DSC was used to compare the spatial overlap between the region of thermal damage as predicted by the models for in vivo normal canine brain during thermal therapy to the region of thermal damage as revealed by contrast-enhanced T1-weighted images acquired immediately after therapy (< 20 min). The outer edge of the hyperintense rim of the ablation region was used as the surrogate marker for the limits of thermal coagulation. The DSC was also used to investigate the impact of varying the thresholds on each models' ability to predict the zone of thermal necrosis.
At previously reported thresholds, the authors found that all three models showed good agreement (defined as DSC > 0.7) with post-treatment imaging. All three models examined across the range of commonly applied thresholds consistently showed highly accurate spatial overlap, low variability, and little dependence on temperature uncertainty. DSC values corresponding to cited thresholds were not significantly different from peak DSC values.
Thus, the authors conclude that the all three thermal dose models can be used as a reliable surrogate for postcontrast tissue damage verification imaging in rapid ablation procedures and can also be used to enhance the capability of MRTI to control thermal therapy in real time.
Medical Physics 10/2010; 37(10):5313-21. · 2.83 Impact Factor
