Showing papers in "Technology in Cancer Research & Treatment in 2004"

Nanoshell-enabled photonics-based imaging and therapy of cancer.

Abstract: Metal nanoshells are a novel type of composite spherical nanoparticle consisting of a dielectric core covered by a thin metallic shell which is typically gold. Nanoshells possess highly favorable optical and chemical properties for biomedical imaging and therapeutic applications. By varying the relative the dimensions of the core and the shell, the optical resonance of these nanoparticles can be precisely and systematically varied over a broad region ranging from the near-UV to the mid-infrared. This range includes the near-infrared (NIR) wavelength region where tissue transmissivity peaks. In addition to spectral tunability, nanoshells offer other advantages over conventional organic dyes including improved optical properties and reduced susceptibility to chemical/thermal denaturation. Furthermore, the same conjugation protocols used to bind biomolecules to gold colloid are easily modified for nanoshells. In this article, we first review the synthesis of gold nanoshells and illustrate how the core/shell ratio and overall size of a nanoshell influences its scattering and absorption properties. We then describe several examples of nanoshell-based diagnostic and therapeutic approaches including the development of nanoshell bioconjugates for molecular imaging, the use of scattering nanoshells as contrast agents for optical coherence tomography (OCT), and the use of absorbing nanoshells in NIR thermal therapy of tumors.

Lighting up tumors with receptor-specific optical molecular probes.

Abstract: Accurate and rapid detection of tumors is of great importance for interrogating the molecular basis of cancer pathogenesis, preventing the onset of complications, and implementing a tailored therapeutic regimen. In this era of molecular medicine, molecular probes that respond to, or target molecular processes are indispensable. Although numerous imaging modalities have been developed for visualizing pathologic conditions, the high sensitivity and relatively innocuous low energy radiation of optical imaging method makes it attractive for molecular imaging. While many human diseases have been studied successfully by using intrinsic optical properties of normal and pathologic tissues, molecular imaging of the expression of aberrant genes, proteins, and other pathophysiologic processes would be enhanced by the use of highly specific exogenous molecular beacons. This review focuses on the development of receptor-specific molecular probes for optical imaging of tumors. Particularly, bioconjugates of probes that...

Near infrared spectroscopy and imaging to probe differences in water content in normal and cancer human prostate tissues.

Abstract: The content of water in cancerous and normal human prostate in vitro tissues was shown to be different using near infrared (NIR) spectroscopy. The water absorption peaks at 1444 nm and 1944 nm are observed in both types of prostate tissues. The measurements show that less water is contained in cancerous tissues than in normal tissues. The OH stretching vibrational overtone mode at 1444 nm and other water overtone modes provide key spectroscopic fingerprints to detect cancer in prostate tissue. Transmission and backscattered spectral imaging were measured in cancer and normal prostate tissues. The degree of polarization for 700 nm, 800 nm, 1200 nm, and 1450 nm is larger for normal than for cancer tissues. The knowledge about water content offers a potential as a diagnostic tool to better determine and image cancer in prostate and in other tissues types such as breast and cervix using the absorption from vibrational overtones of H(2)O molecules in the NIR.

The role of diffusion tensor imaging in establishing the proximity of tumor borders to functional brain systems: implications for preoperative risk assessments and postoperative outcomes.

Abstract: Diffusion Tensor Imaging (DTI) is a new MRI imaging technique sensitive to directional movements of water molecules, induced by tissue barriers. This provides a new form of contrast that allows the identification of functional white matter tracts within the brain, and has been proposed as a technique suitable for presurgical planning in brain tumor patients. Resection of primary brain tumors improves survival, functional performance, and the effectiveness of adjuvant therapies, provided that surgically-induced neurological deficits can be avoided. Diffusion Tensor Imaging (DTI) has the potential to establish spatial relationships between eloquent white matter and tumor borders, provide information essential to preoperative planning, and improve the accuracy of surgical risk assessments preoperatively. We present our experience in a series of 28 brain tumor patients where the integration of functional magnetic resonance imaging (fMRI) and DTI data was used to determine key anatomic spatial relationships preoperatively. Twice as many functional systems were localized to within 5 mm of tumor borders when DTI and fMRI were utilized for preoperative planning, compared to that afforded by fMRI alone. Our results show that the combined use of fMRI and DTI can provide a better estimation of the proximity of tumor borders to eloquent brain systems sub-serving language, speech, vision, motor and premotor functions. Additionally, a low regional complication rate (4%) observed in our series suggests that preoperative planning with these combined techniques may improve surgical outcomes compared to that previously reported in the literature. Larger studies specifically designed to establish the accuracy and predictive value of DTI in brain tumor patients are warranted to substantiate our preliminary observations.

Serum interleukin-8 is elevated in men with prostate cancer and bone metastases.

Abstract: Aalinkeel et al. (1) have recently reported that gene expression of angiogenic factors correlates with metastatic potential of prostate cancer cells. The rationale for the study of Aalinkeel et al. is that a variety of growth factors, among them interleukin-8 (il-8), can induce angiogenesis (2). Further, parathyroid hormone related peptide (PTHrP) acts to induce il-8 production in prostate cancer cells via an intracrine pathway independent of its classical nuclear localization sequence. This novel pathway could mediate the effects of PTHrP on the progression of prostate cancer (3). We measured il-8 in the serum of 39 men with biopsy-proven prostate cancer. Their average age was 69 +/- 9 (mean +/- SD). Serum il-8 was measured with an automated chemiluminometric high sensitivity il-8 protein assay (Immulite, Diagnostic Products Corporation, Los Angeles, CA). We noted a significant elevation of il-8 in men with bone metastases, diagnosed by Tc-99 MDP bone scan, when compared to men with localized disease (Figure 1). Aalinkeel et al. found that il-8 was significantly higher in the more metastatic PC-3 and DU-145 prostate cancer cell lines, when compared to the poorly metastatic LnCAP cells. The results of our study of il-8 in men with prostate cancer support the findings of Aalinkeel et al. Therefore, new anti-angiogenic therapies targeting specific genes controlling prostate tumor metastasis may be of benefit in treating prostate cancer.

Combination of digital mammography with semi-automated 3D breast ultrasound.

Abstract: This paper describes work aimed at combining 3D ultrasound with full-field digital mammography via a semi-automatic prototype ultrasound scanning mechanism attached to the digital mammography system gantry. Initial efforts to obtain high x-ray and ultrasound image quality through a compression paddle are proving successful. Registration between the x-ray mammogram and ultrasound image volumes is quite promising when the breast is stably compressed. This prototype system takes advantage of many synergies between the co-registered digital mammography and pulse-echo ultrasound image data used for breast cancer detection and diagnosis. In addition, innovative combinations of advanced US and X-ray applications are being implemented and tested along with the basic modes. The basic and advanced applications are those that should provide relatively independent information about the breast tissues. Advanced applications include x-ray tomosynthesis, for 3D delineation of mammographic structures, and non-linear elasticity and 3D color flow imaging by ultrasound, for mechanical and physiological information unavailable from conventional, non-contrast x-ray and ultrasound imaging.

Repositioning accuracy of a commercially available double-vacuum whole body immobilization system for stereotactic body radiation therapy.

Abstract: We evaluated the repositioning accuracy of a commercially available stereotactic whole body immobilization system (BodyFIX, Medical Intelligence, Schwabmuenchen, Germany) in 36 patients treated by hypofractionated stereotactic body radiation therapy. CT data were acquired for positional control of patient and tumor before each fraction of the treatment course. Those control CT datasets were compared with the original treatment planning CT simulation and analyzed with respect to positional misalignment of bony patient anatomy, and the respective position of the treated small lung or liver lesions. We assessed the stereotactic coordinates of distinct bony anatomical landmarks in the original CT and each control dataset. In addition, the target isocenter was recorded in the planning CT simulation dataset. An iterative optimization algorithm was implemented, utilizing a root mean square scoring function to determine the best-fit orientation of subsequent sets of anatomical landmark measurements relative to th...

Cryosurgery for lung cancer: clinical results and technical aspects.

Abstract: Lung carcinoma is the most frequently diagnosed malignancy in the world, with the incidence increasing through the 20th century. Presentation may be as a tumor mass primarily obstructing the central bronchial lumen, or a mass infiltrating lung tissue. Cryosurgery can be used as a method of palliative treatment for both these endobronchial and extrabronchial presentations. The aim of this study is two-fold: to present data relating to our extensive experience in treating obstructing endobronchial tumors and to present our initial results of direct cryosurgery to infiltrating lung tumor masses. During a nine-year period, 521 consecutive patients (male:female ratio 1.8:1) with a mean age of 67.9 years who had advanced obstructive tracheobronchial malignant tumors underwent cryosurgery with a mean of 2.4 treatments per patient. Hemoptysis, cough, dyspnoea and chest pain improved by at least one class in 76.4%, 69.0%, 59.25% and 42.6% (p<0.01) of symptomatic patients respectively. Quality of life studies showed that the mean Karnofsky score improved from 60 +/- 7 to 75 +/- 8 and the mean WHO score from 3.04 +/- 0.7 to 2.20 +/- 0.56. There were 7 (1.2%) in-hospital deaths, and 2-year survival was 15.9%. Direct cryosurgery to carcinoma of the lung was performed on 15 patients at exploratory thoracotomy. Results showed an increase in FEV1 from 1.80 +/- 0.6 liters to 1.95 +/- 0.8 (8.3%) liters and in FVC from 2.50 +/- 0.8 to 2.68 +/- 0.8 liters (7.2%). The Karnofsky score improved from 68 +/- 9 to 78 +/- 10 and the WHO score from 2.63 +/- 0.81 to 2.38 +/- 0.78 (9.6%). Major symptoms including cough, dyspnoea, and hemoptysis were assessed and showed improvement in 77.8%, 66.7%, and 100% (p<0.01) of symptomatic patients respectively. Patients were followed for a mean period of 18 months (range 4-84 months). Median survival from the date of surgery (Kaplan-Meier, 95%Cl) was 11.6 (6.8 to 18.2) months, range 1 to 84 months. Cryosurgery provides a safe and effective method for the palliation of advanced central bronchial obstructive tumors, and compares favorably with other methods in terms of safety, cost, and complications. Initial experience suggests that similar palliation may be achieved by cryosurgery applied to advanced parenchymal tumor masses.

Imaging of the ovary.

Abstract: Epithelial ovarian cancer has the highest mortality rate among the gynecologic cancers and spreads beyond the ovary in 90% of the women diagnosed with ovarian cancer. Detection before the disease has spread beyond the ovary would significantly improve the survival from ovarian cancer, which is currently only 30% over 5 years, despite extensive efforts to improve the survival. This study describes initial investigation of the use of optical technologies to improve the outcome for this disease by detecting cancers at an earlier and more treatable stage. Women undergoing oophorectomy were recruited for this study. Ovaries were harvested for fluorescence spectroscopy, confocal microscopy, and optical coherence tomography. Fluorescence spectroscopy showed large diagnostic differences between normal and abnormal tissue at 270 and 340 nm excitation. Optical coherence tomography was able to image up to 2mm deep into the ovary with particular patterns of backscattered intensity observed in normal versus abnormal tissue. Fluorescence confocal microscopy was able to visualize sub-cellular structures of the surface epithelium and underlying cell layers. Optical imaging and/or spectroscopy has the potential to improve the diagnostic capability in the ovary, but extended systematic investigations are needed to identify the unique signatures of disease. The combination of optical technologies supported by modern molecular biology may lead to an instrument that can accurately detect early carcinogenesis.

Resolution and contrast in magnetic resonance electrical impedance tomography (MREIT) and its application to cancer imaging.

Abstract: It has been reported that the electrical impedance of malignancies could be 20-40 times lower than healthy tissues and benign formations. Therefore, in vivo impedance imaging of suspicious lesions may prove to be helpful in improving the sensitivity and specificity of detecting malignant tumors. Several systems have been developed to map the conductivity distribution inside a volume of tissue, however they suffer from poor spatial resolution because the measurements are taken only from surface electrodes. MRI based impedance imaging (MREIT) is a novel method, in which weak electrical currents are injected into the tissue and the resulting perturbations in the magnetic field are measured using MRI. This method has been shown to provide better resolution compared to previous techniques of impedance imaging because the measurements are taken from inside the object on a uniform grid. Thus, it has the potential to be a useful modality that may detect malignancies earlier. Several phantom imaging experiments were performed to investigate the spatial resolution and dynamic range of contrast of this technique. The method was also applied to a live rat bearing a R3230 AC tumor. Tumor location was identified by contrast enhanced imaging.

Progress toward optimization of cryosurgery.

Abstract: Cryosurgery for diverse neoplastic and non-neoplastic diseases has expanded in applicability in recent years, especially since intraoperative ultrasound became available as a method of monitoring the process of tissue freezing. However, persistence of disease after presumably adequate cryosurgical treatment has disclosed deficiencies in the technique, perhaps due to faulty application of the freeze-thaw cycles or due to shortcomings in the imaging method. Clearly cryosurgical technique is less than optimal. The optimal dosimetry for tissue freezing, the recent improvements in imaging techniques, and the need for adjunctive therapy are defined in this review, which assesses the progress toward improving the efficacy of cryosurgery.

Nanoparticle Based Systemic Gene Therapy for Lung Cancer: Molecular Mechanisms and Strategies to Suppress Nanoparticle-Mediated Inflammatory Response:

Abstract: Cancer gene therapy for the treatment of lung cancer has shown promise in the laboratory and in Phase I/II clinical trials. However, it is currently limited to treating localized tumors due to host-immunity against the gene delivery vector and the transgene. Therefore, there is a tremendous effort to develop and test alternate gene delivery vectors that are efficient, non-immunogenic, and applicable for systemic therapy. One such gene delivery vehicle is the non-viral vector, DOTAP:cholesterol (DOTAP:Chol) nanoparticle. Preclinical studies from our laboratory has shown that DOTAP:Chol. nanoparticles are effective systemic gene delivery vectors that efficiently deliver tumor-suppressor genes to disseminated lung tumors. Based on our findings we have recently initiated a Phase-I trial for systemic treatment of lung cancer using a novel tumor suppressor gene, FUS1. Although DOTAP:Chol. nanoparticles complexed to DNA (DNA-nanoparticles) are efficient vectors for systemic therapy, induction of an inflammatory response in a dose-dependent fashion has also been observed thereby limiting its use. A better understanding of the underlying mechanism for DNA-nanoparticles-mediated inflammatory response will allow us to develop strategies to suppress inflammation and expand the therapeutic window in treating human cancer. In the present study we conducted experiments examining the mechanism of nanoparticle-mediated inflammatory response in vitro and in vivo. We demonstrate that systemic administration of DNA-nanoparticles induced multiple signaling molecules both in vitro and in vivo that are associated with inflammation. Use of small molecule inhibitors against the signaling molecules resulted in their suppression and thereby reduced inflammation without affecting transgene expression. Our results provide a rationale to use small molecule inhibitors to suppress nanoparticle-mediated inflammation when administered systemically. Further development and testing will allow us to incorporate this strategy into future clinical trials that is based on systemic non-viral vector gene therapy.

Fluorescence imaging in vivo: raster scanned point-source imaging provides more accurate quantification than broad beam geometries.

Abstract: Two fluorescence imaging systems were compared for their ability to quantify mean fluorescence intensity from surface-weighted imaging of tissue. A broad beam CCD camera system was compared to a point sampling system that raster scans to create the image. The effects of absorption and scattering in the background tissue volume were shown to be similar in their effect upon the signal, but the effect of the three-dimensional shape of the tissue was shown to be a significant distortion upon the signal. Spherical phantoms with Intralipid and blood for absorber and scatterer were used with a fixed concentration of aluminum phthalocyanine fluorophore to illustrate that the mean intensity observed with the broad beam system increased with size, while the mean intensity observed with the raster scanned system was not as significantly affected. Similar results were observed in vivo with mice injected with the fluorophore and imaged multiple times to observe the pharmacokinetics of the drug. The fluorescence in the...

The male lumpectomy: rationale for a cancer targeted approach for prostate cryoablation. A review.

Abstract: Lumpectomy to treat breast cancer has revolutionized the management of that disease. Lumpectomy showed that the quality of life of the individual patient can successfully be integrated into the equation of cancer treatment, without major loss of cancer treatment efficacy. Prostate cancer raises many of the same issues that breast cancer does in women. Impotence and incontinence, affects the male self image and psyche no less than the loss of a breast does a woman. Management of prostate cancer ranges from no treatment at all ("watchful waiting") to treatments in which the whole gland is destroyed (radiation therapy, cryosurgery) or removed (radical prostatectomy), with presently no treatment in between these extremes. Pathologic literature indicates, however, that 35% of prostate cancers are solitary and unilateral. In addition, long term studies have confirmed that cryoabltion for prostate cancer is an efficacious treatment. In this paper we will examine the rationale for a "male lumpectomy" using cryoablation and present preliminary data supporting it's role in prostate cancer management.

Cryosurgery for tumors - a clinical overview.

Abstract: Cryosurgery, a method of treating disease by the production of freezing temperatures in the tissue, is a useful technique for the treatment of tumors. When the modern era of cryosurgery began in the mid 1960's, the technique was used only for tumors easily accessible by direct observation or via endoscopy, such as those of the skin, oral cavity, and prostate gland. In general, the technique had limited usefulness in the next two decades. However, with the advent of intraoperative ultrasound as a method of monitoring the process of freezing and with the development of more effective cryosurgical apparatus, the cryosurgical treatment of tumors of the viscera and other deep tissues became practical in the 1990's. This review assesses the present day status of cryosurgery in the management of diverse tumors.

Cryotherapy for liver tumors: current status, perspectives, clinical results, and review of literature.

Abstract: Cryotherapy has gained importance as a locally ablative treatment option for patients with non-resectable liver tumors, especially metastases from colorectal cancer. We have used this technique since 1996 for the treatment of 77 patients with malignant liver tumors. Patient data was prospectively recorded and follow-up was until September 2002 or death. Fifty-five patients had colorectal cancer liver metastases, 16 metastases from other primaries and 6 had hepatoma. Forty patients had cryotherapy only and 37 had an additional liver resection. Morbidity and mortality were 22% and 1.3%, respectively.In 68% of patients with colorectal liver metastases and an elevated serum carcinoembryonic antigen-level preoperatively, it returned to the normal range following cryosurgery. For all 77 patients, median survival was 28 months with a 3- and 5-year-survival rate of 39% and 26%, respectively, and median survival was 29 months with a 3- and 5-year-survival rate of 44% and 26%, respectively, for the 55 patients with...

The Imaging of Apoptosis with the Radiolabeled Annexin V: Optimal Timing for Clinical Feasibility

Abstract: In recent years, the imaging of drug-induced apoptosis has become one of the centers of interest in experimental and clinical research. In particular, the accurate monitoring of chemosensitivity as well as the early prediction of chemoresistance in response to various pro-apoptotic interventions are critical requirements for the best management of oncology patients. The use of technetium [(99m)Tc]-labeled annexin V on animal and human models of cancers provides a proof of principle for the feasibility of a non-invasive, in vivo detection of an apoptotic signal and then for the early assessment of tumor response in the course of chemotherapy. Although promising, however, the initial clinical data point out on the technical limitations that are still to be resolved in terms of tumor-to-background ratio and optimal timing for the imaging of apoptosis. In the present review article, we report the results of animal studies aimed to the evaluation of apoptotic peaks following chemotherapy. In the light of these basic research works, we analyze the profiles of radiolabeled annexin V uptake over time as observed in clinical trials. We then discuss possible new imaging strategies designed to optimize the visualization of apoptotic changes within tumor tissues using the [(99m)Tc]-labeled annexin V. We also suggest longer lived forms of radiolabeled annexin V designed to better understand the temporal patterns of apoptotic tumor response, which in turn, may help to capture the best time-window for the imaging of cell death.

Characteristic absorbance of nucleic acids in the Mid-IR region as possible common biomarkers for diagnosis of malignancy.

Abstract: FTIR spectroscopy has been extensively used to understand the differences between normal and malignant cells and tissues. In the present study, FTIR microspectroscopy was performed on biopsies to evaluate parameters deduced from changes in nucleic acid absorbance monitored at various characteristic wavenumbers in the Mid-IR region. The data showed that there were differences in the spectra of normal and malignant tissues from several organs such as colon, cervix, skin and blood with respect to absorbance due to nucleic acids. Similar results were observed in the case of cell lines that were transformed to induce carcinogenesis. Of the several ratios examined for consistency in differentiating cancer and normal tissues, the I(996 cm−1)/I(966 cm−1) showed promise as a distinguishing parameter and was comparable to the I(1121 cm−1)/I(1020 cm−1) ratio reported in many earlier studies. The absorbance of nucleic acids is presented with an emphasis on the application of FTIR microspectroscopy for diagnosis of ma...

Differentiating surgical from non-surgical lesions using perfusion MR imaging and proton MR spectroscopic imaging

Abstract: Advanced MRI techniques, such as MR spectroscopy, diffusion and perfusion MR imaging can give important in vivo physiological and metabolic information, complementing morphologic findings from conventional MRI in the clinical setting. Combining perfusion MRI and MR spectroscopy can help in patients with brain masses in who the pre-operative differential diagnosis is unclear. This review demonstrates the use of dynamic, susceptibility weighted, contrast-enhanced MR imaging (DSC MRI) and magnetic resonance spectroscopic imaging (MRSI) to distinguish surgical from non-surgical lesions in the brain. There is overlap in the MRI appearance of many enhancing and ring-enhancing lesions such as gliomas, metastases, inflammatory lesions, demyelinating lesions, subacute ischemia, abscess and some AIDS related lesions. We review examples of histopathologically confirmed high-grade glioma, a middle cerebral artery territory infarct, a tumefactive demyelinating lesion and a metastasis for which conventional MR imaging (MRI) was non-specific and potentially misleading and demonstrate how DSC MRI and MRSI features were used to increase the specificity of neurodiagnosis. At several institutions, many patients routinely undergo MRI as well as MRSI and DSC MRI. Cerebral blood flow (CBF), mean transit time (MTT), and relative cerebral blood volume (rCBV) measurements are obtained from regions of maximal perfusion as determined from perfusion color overlay maps. Metabolite levels and ratios are determined for Choline (Cho), N-Acetyl Aspartate (NAA), Lactate and Lipids (LL). Metabolite levels are obtained by measuring the peak heights of each metabolite and the ratios are obtained from these measurements for Cho/Cr, Cho/NAA and NAA/Cr. Neurosurgical intervention carries substantial morbidity, mortality, financial and potential emotional cost to the patient and family. Making a pre-operative diagnosis allows the neurosurgeon to be confident in the choice of treatment plan for the patient and allays considerable patient anxiety. The utility of combining clinical findings with multi-parametric information from perfusion and spectroscopic MR imaging in differentiating surgical lesions from those which do not require surgical intervention is discussed.

Inversely planned intensity modulated radiotherapy of the breast including the internal mammary chain: a plan comparison study.

Abstract: The aim of this paper is to evaluate the benefit of inversely planned intensity modulated radiotherapy (IMRT) in the adjuvant irradiation of breast cancer when internal mammary lymph nodes are included in the treatment volume. 20 patients treated with 3D-planned conventional radiotherapy (CRT) following breast conserving surgery were included in the study. We chose 10 patients with left-sided and 10 patients with right-sided tumors. All treatment volumes included the internal mammary chain. For plan comparison to the applied CRT plan an inverse IMRT-plan in, step-and-shoot'-technique was calculated. For all patients IMRT resulted in an improved conformity of dose distribution to the target volume compared to CRT (mean COIN95: 0.798 vs. 0.514 with COIN95 = C1 * C2 (C1= fraction of CTV that is covered by > 95% of the prescribed dose and C2 = volume of CTV that is covered by > 95% of the prescribed dose/total volume that is covered by > 95% of the prescribed dose). In all cases with matching adjacent beams, the homogeneity in the target volume was improved. The volume of the ipsilateral lung irradiated with a dose higher than 20 Gy was reduced with IMRT from 24.6% to 13.1% compared to CRT. For left-sided target volume the heart volume with a dose higher than 30 Gy was reduced from 6.2% to 0.2%. The presented plan comparison study for irradiation of the breast and the parasternal lymph nodes showed a substantial improvement of the dose distribution by inversely planned IMRT compared to CRT. This is visible for the target volume, the ipsilateral lung and, in case of left-sided target volume, the heart. Despite an increase in integral dose to the entire normal tissue, the application of IMRT might be clinically advantageous in cases where no satisfying dose distribution can be obtained by CRT.

Helical tomotherapy as a means of delivering accelerated partial breast irradiation.

Abstract: A novel treatment approach utilizing helical tomotherapy for partial breast irradiation for patients with early-stage breast cancer is described. This technique may serve as an alternative to high dose-rate (HDR) interstitial brachytherapy and standard linac-based approaches. Through helical tomotherapy, highly conformal irradiation of target volumes and avoidance of normal sensitive structures can be achieved. Unlike HDR brachytherapy, it is noninvasive. Unlike other linac-based techniques, it provides image-guided adaptive radiotherapy along with intensity modulation. A treatment planning CT scan was obtained as usual on a post-lumpectomy patient undergoing HDR interstitial breast brachytherapy. The patient underwent catheter placement for HDR treatment and was positioned prone on a specially designed position-supporting mattress during CT. The planning target volume (PTV) was defined as the lumpectomy bed plus a 20 mm margin. The prescription dose was 34 Gy (10 fx of 3.4 Gy) in both the CT based HDR and on the tomotherapy plan. Cumulative dose-volume histograms (DVHs) were generated and analyzed for the target, lung, heart, skin, pectoralis muscle, and chest wall for both HDR brachytherapy and helical tomotherapy. Dosimetric coverage of the target with helical tomotherapy was conformal and homogeneous. "Hot spots" (> or =150% isodose line) were present around implanted dwell positions in brachytherapy plan whereas no isodose lines higher than 109% were present in the helical tomotherapy plan. Similar dose coverage was achieved for lung, pectoralis muscle, heart, chest wall and breast skin with the two methods. We also compared our results to that obtained using conventional linac-based three dimensional (3D) conformal accelerated partial breast irradiation. Dose homogeneity is excellent with 3D conformal irradiation, and lung, heart and chest wall dose is less than for either HDR brachytherapy or helical tomotherapy but skin and pectoral muscle doses were higher than with the other techniques. Our results suggest that helical tomotherapy can serve as an effective means of delivering accelerated partial breast irradiation and may offer superior dose homogeneity compared to HDR brachytherapy.

Quantitative pathology in tissue MR spectroscopy based human prostate metabolomics.

Abstract: At present, the clinical utility of metabolomic profiles of human prostate tissue relies on the establishment of correlations between metabolite data and clinical measurements, particularly patholo...

Ultrasound guided combined cryoablation and microencapsulated 5-Fluorouracil inhibits growth of human prostate tumors in xenogenic mouse model assessed by luminescence imaging.

Abstract: Modern approaches to minimally invasive ablative treatment of solid tumors involve the use of miniature instruments and combined treatments. These can be enhanced with ultrasound imaging that depic...

Quantitative assessment of tumor vasculature and response to therapy in kaposi's sarcoma using functional noninvasive imaging.

Abstract: Two noninvasive methods, thermography and laser Doppler imaging (LDI), were assessed for their ability to quantitatively assess parameters of vascularity in lesions of HIV-associated Kaposi's sarcoma (KS). Thermography and LDI images of a representative KS lesion were recorded in 16 patients and compared to normal skin either adjacent to the lesion or on the contralateral side. Eleven of the 16 patients had greater than 0.5 degrees C increased temperature and 12 of the 16 patients had increased flux (measured by LDI) as compared to normal skin. There was a strong correlation between these two parameters (R = 0.81, p < 0.001). In ten patients, measurements were obtained prior to therapy and after receiving a regimen of liposomal doxorubicin and interleukin-12. After 18 weeks of therapy, temperature and blood flow of the lesions were significantly reduced from the baseline (p = 0.004 and 0.002 respectively). These techniques hold promise to assess physiologic parameters in KS lesions and their changes with therapy.

Computerized Planning of Cryosurgery Using Cryoprobes and Cryoheaters

Abstract: In a typical minimally invasive cryoprocedure, multiple cryoprobes are inserted into the tissue with the goal of maximizing cryoinjury within a predefined target region, while minimizing cryoinjury to the surrounding tissues. A temperature-controlled electrical heater has been developed recently by this research team, in order to assist in limiting the cryoinjury to the target region. The new device has been termed a 'cryoheater,' and it can work with any cryosurgical cooling technique. A prototype computerized planning tool has been presented recently by this research team, which helps to determine the best locations in which to insert the cryoprobes. This prototype was designed for cryoprobes only. The planning procedure utilized a novel iterative optimization technique, based on a force-field analogy. The combination of cryoheaters with computerized planning is the subject matter of this report. The current report includes a review of cryoheater development, and presents an improved cryosurgery planning tool which incorporates cryoheaters.

High dose rate brachytherapy: its clinical applications and treatment guidelines.

Abstract: Brachytherapy has the advantage of delivering a high dose to the tumor while sparing the surrounding normal tissues. With proper case selection and delivery technique, high-dose-rate (HDR) brachytherapy has great promise, because it eliminates radiation exposure, allows short treatment times, and can be performed on an outpatient basis. Additionally, use of a single-stepping source, allows optimization of dose distribution by varying the dwell time at each dwell position. However, when HDR brachytherapy is used, the treatments must be executed carefully, because the short treatment times do not allow any time for correction of errors, and mistakes can result in harm to patients. Hence, it is very important that all personnel involved in HDR brachytherapy be well trained and be constantly alert.It is expected that the use of HDR brachytherapy will greatly expand over the next decade and that refinements will occur primarily in the integration of imaging (computed tomography, magnetic resonance imaging, int...

Multiparametric and multinuclear magnetic resonance imaging of human breast cancer: current applications.

Abstract: The exploration of novel imaging methods that have the potential to improve specificity for the identification of malignancy is still critically needed in breast imaging. Changes in physiologic alterations of soft tissue water associated with breast cancer can be visualized by magnetic resonance (MR) imaging. However, it is unlikely that a single MR parameter can characterize the complexity of breast tissue. Techniques such as multiparametric MR imaging, proton magnetic resonance spectroscopic (MRSI) imaging, and 23Na sodium MR imaging when used in combination provide a comprehensive data set with potentially more power to diagnose breast disease than any single measure alone. A combination of MR, MRSI, and 23Na sodium MR parameters may be examined in a single MR imaging examination, potentially resulting in improved specificity for radiologic evaluation of malignancy.

Improved display of synthetic IgG-binding domains on the baculovirus surface.

Abstract: Improved display of foreign protein moieties in combination with beneficial alteration of the viral surface properties should be of value for targeted and enhanced gene delivery. Here, we describe a vector based on Autographa californica multiple nucleopolyhedrovirus (AcMNPV) displaying synthetic IgG-binding domains (ZZ) of protein A fused to the transmembrane anchor of vesicular stomatitis virus (VSV) G protein. This display vector was equipped with a GFP/EGFP expression cassette enabling fluorescent detection in both insect and mammalian cells. The virus construct displayed the biologically active fusion protein efficiently and showed increased binding capacity to IgG. As the display is carried out using a membrane anchor of foreign origin, gp64 is left intact for virus entry, which may increase gene expression in the transduced mammalian cells. In addition, the viral vector can be targeted to any desired cell type via binding of ZZ domains when an appropriate IgG antibody is available.

Abnormal vessel tortuosity as a marker of treatment response of malignant gliomas: preliminary report.

Abstract: Despite multiple advances in medical imaging, noninvasive monitoring of therapeutic efficacy for malignant gliomas remains problematic. An underutilized observation is that malignancy induces characteristic abnormalities of vessel shape. These characteristic shape abnormalities affect both capillaries and much larger vessels in the tumor vicinity, involve larger vessels prior to sprout formation, and are generally not present in hypervascular benign tumors. Vessel shape abnormalities associated with malignancy thus may appear independently of increase in vessel density. We hypothesize that an automated, computerized analysis of vessel shape as defined from high-resolution MRA can provide valuable information about tumor activity during the treatment of malignant gliomas. This report describes vessel shape properties in 10 malignant gliomas prior to treatment, in 2 patients in remission during treatment, and in 2 patients with recurrent disease. One subject was scanned multiple times. The method involves an automated, statistical analysis of vessel shape within a region of interest for each tumor, normalized by the values obtained from the vessels within the same region of interest of 34 healthy subjects. Results indicate that untreated tumors display statistically significant vessel tortuosity abnormalities. These abnormalities involve vessels not only within the tumor margins as defined from MR but also vessels in the surrounding tissue. The abnormalities resolve during effective treatment and recur with tumor recurrence. We conclude that vessel shape analysis could provide an important means of assessing tumor activity.

Computerized detection of mass lesions in digital breast tomosynthesis images using two- and three dimensional radial gradient index segmentation.

Abstract: Initial results for a computerized mass lesion detection scheme for digital breast tomosynthesis (DBT) images are presented. The algorithm uses a radial gradient index feature for the initial lesion detection and for segmentation of lesion candidates. A set of features is extracted for each segmented partition. Performance of two- and three dimensional features was compared. For gradient features, the additional dimension provided no improvement in classification performance. For shape features, classification using 3D features was improved compared to the 2D equivalent features. The preliminary overall performance was 76% sensitivity at 11 false positives per exam, estimated based on DBT image data of 21 masses. A larger database will allow for further development and improvement in our computer aided detection scheme.