bluuebunny/crossref_metadata_2025 huggingface dataset:
Image Guided Stereotactic Radiosurgery for Lesions in Proximity to the Anterior Visual Pathways: A Preliminary Report
Authors: Mehta Vivek K. , Le Quynh-Thu , Chang Steven D. , Chenery Stafford , Adler John R.
Published: October 2014

The incidence of optic neuropathy after stereotactic radiosurgery (SRS) is related to the total dose, fraction size, and treatment volume. Theoretically, fractionated SRS can decrease this risk. In this paper, we report our technique for fractionated SRS and assess its potential role in the management of tumors located adjacent to the anterior visual pathways. Since 1997, thirteen patients (median age: 50, range 21–76) with lesions in close proximity to the anterior visual pathways were treated on the CyberKnife image guided SRS system (Accuray, Inc., Sunnyvale, CA). The CyberKnife is a 6MV linear accelerator mounted on a robotic arm which can monitor and adjust to changes in the target position in real time thus eliminating skeletal frame immobilization and allowing for convenient multi-fraction SRS treatments. Magnetic Resonance Imaging (MRI) and computerized tomography (CT) imaging for treatment planning were obtained with the patient's head immobilized in an aquaplast mask. After image fusion, the target and critical structures were delineated. Two to five fractions were prescribed with approximately a 24-hour interfraction interval. The patients received 25 Gy in 5 fractions (n=5), 21 Gy in 3 fractions (n=5), or 20 Gy in 2 fractions (n=3) to the 75–95% isodose line. Ten of the thirteen patients had good pretreatment vision. In nearly all instances, the volume of the optic nerve that received 80% of the prescribed dose was < 0.05 cm3. In all instances, the volume of the optic nerve that received 50% of the prescribed dose was ≤ 0.5 cm3. Only one patient received more than a 5 Gy daily dose to > 0.03 cm3 of optic nerve. With median follow up of 18 months (range 12 to 54), four patients have had improvement in their vision. No visual deterioration has been observed in any of the other patients. In addition, there has been no tumor progression within the treated field. Fractionated SRS using the CyberKnife is technically feasible and may decrease the risk of optic neuropathy. Greater patient accrual and longer follow up will be necessary to further determine the clinical benefit of this approach.
Clinical Proteomics for Cancer Biomarker Discovery and Therapeutic Targeting
Authors: Krieg Rene C. , Paweletz Cloud P. , Liotta Lance A. , Petricoin Emanuel F.
Published: October 2014

As we emerge into the post-genome era, proteomics finds itself as the driving force field as we translate the nucleic acid information archive into understanding how the cell actually works and how disease processes operate. Even so, the traditionally held view of proteomics as simply cataloging and developing lists of the cellular protein repertoire of a cell are now changing, especially in the sub-discipline of clinical proteomics. The most relevant information archive to clinical applications and drug development involves the elucidation of the information flow of the cell; the “software” of protein pathway networks and circuitry. The deranged circuitry of the cell as the drug target itself as well as the effect of the drug on not just the target, but also the entire network, is what we now are striving towards. Clinical proteomics, as a new and most exciting sub-discipline of proteomics, involves the bench-to-bedside clinical application of proteomic tools. Unlike the genome, there are potentially thousands of proteomes: each cell type has its own unique proteome. Moreover, each cell type can alter its proteome depending on the unique tissue microenvironment in which it resides, giving rise to multiple permutations of a single proteome. Since there is no polymerase chain reaction equivalent to proteomics- identifying and discovering the “wiring diagram” of a human diseased cell in a biopsy specimen remains a daunting challenge. New micro-proteomic technologies are being and still need to be developed to drill down into the proteomes of clinically relevant material. Cancer, as a model disease, provides a fertile environment to study the application of proteomics at the bedside. The promise of clinical proteomics and the new technologies that are developed is that we will detect cancer earlier through discovery of biomarkers, we will discover the next generation of targets and imaging biomarkers, and we can then apply this knowledge to patient-tailored therapy.
SELDI ProteinChip® Array in Oncoproteomic Research
Authors: Yip Tai-Tung , Lomas Lee
Published: October 2014

Research into the causes, early detection and treatment of cancers is a primary focus of the health care industry and proteomic-based methodologies are providing an increasingly important role in addressing these issues. The ProteinChip® Array technology forms the basis of a clinical proteomics platform designed to expedite the discovery, validation, and characterization of cancer biomarkers at all stages of cancer progression. Being able to detect cancer progression early in turn allows for the possibility of more effective treatment. This short review serves to introduce the technology by highlighting specific examples related to cancer biomarker discoveries.
Applications of Plasmid Electrotransfer
Authors: Scherman Daniel , Bigey Pascal , Bureau Michel Francis
Published: October 2014

The use of electric pulses to transfect cells has recently been extended to show the utility of this procedure in vivo. Electrotransfer has been performed in vivo on several tissue types including skin, blood vessels, liver, tumor, muscle, cornea, brain and spleen. The most widely targeted tissue has been skeletal muscle. In addition to its potential use in gene therapy, in vivo DNA electrotransfer is also, because of its simplicity, a powerful laboratory tool to study in vivo gene expression and function in a given tissue. Many published studies have now shown that plasmid electrotransfer can lead to a long-lasting therapeutic effect in various pathologies, such as cancer, blood disease, or muscle ischemia. The future potential for this gene therapy approach will include delivery for both local action or distal effect by secretion of the transgenic proteins in the circulation.
Electrical Enhancement of Formulated Plasmid Delivery in Animals
Authors: Draghia-Akli Ruxandra , Khan Amir S. , Cummings Kathleen K. , Parghi Deena , Carpenter Robert H. , Brown Patricia A.
Published: October 2014

Electroporation has been shown to significantly increase plasmid transfer to the skeletal muscle, but this procedure is also implicated in muscle damage. We are reporting a highly efficient in vivo transfer of a plasmid formulated with poly-(L-glutamate) (PLG) into murine, canine and porcine muscle fibers using electric pulses of low field intensity. In mice and pigs, the use of secreted embryonic alkaline phosphatase (SEAP) as the indicator gene caused increased PLG expression by 2–3 fold compared to naked plasmid; while delivery of a PLG-plasmid formulation to dogs showed a 10-fold increase in serum SEAP levels compared to plasmid alone. Muscle lesions were reduced by the protective PLG. Thus, PLG may constitute a useful adjuvant for increased expression and reduced muscle trauma to plasmid DNA delivered by electroporation.
The Application of Electroporation to Transfect Hematopoietic Cells and to Deliver Drugs and Vaccines Transcutaneously for Cancer Treatment
Authors: Hui Sek-Wen
Published: October 2014

Electroporation and the associated phenomenon of electrofusion have been widely adapted as tools to a broad range of biomedical research and therapy. In this article, we summarize our adaptation of the electroporation and electrofusion technology in two fronts of cancer research and treatment. The first is genetic manipulation of hematopoietic cells for the purpose of cancer treatment. High efficiency transfection methods have been developed to transfect NK cells, peripheral blood stem cells, and bone marrow derived dendritic cells. Hybrids of tumor cells and bone marrow derived dendritic cells have been formed by electrofusion for the purpose of tumor vaccines. The second front is the use of transcutaneous electroporation to deliver anticancer drugs and vaccines across the skin. Methods to extend the upper molecular weight limit of transcutaneous electroporation have been developed. The pro-photosensitizer drug, δ-amino levulinic acid, the anticancer drug methotrexate, and peptide vaccines designed for cancer prevention and immunotherapy have been delivered transcutaneously by electroporation. These studies hold promise for the treatment of cancers in human.
Foreword
Authors: Nalcioglu Orhan , Clarke Laurence
Published: October 2014

In vivo medical imaging has become one of the most important measurement tools in biomedical research and clinical investigations. Medical imaging applications cover a broad spectrum going from small animal research to human studies. This is due to the fact that in vivo medical imaging techniques based on various modalities are capable of providing anatomic, functional, and metabolic information non-invasively with accurate spatial localization enabling longitudinal studies on the same subject. One of the most significant application of such techniques has been in the study of cancer. In this special issue on in vivo medical imaging, we tried to give the readers a flavor of the types of studies that are being done in cancer research and clinical applications. We should emphasize that the topics covered here due to limited space will only provide the readers with a rather limited view. Furthermore, one of the new and upcoming imaging techniques, namely molecular imaging will not be covered here since there have been various extensive reviews of the field have been given in the literature.
On the Incorporation of Multi-Modality Image Registration into the Radiotherapy Treatment Planning Process
Authors: Jaradat Hazim A. , Tomé Wolfgang A. , McNutt Todd R. , Meyerand M. Elizabeth
Published: October 2014

A technique is presented that allows the direct use of physiological image sets in the radiation therapy treatment planning process. When fused to the treatment planning CT, physiological image studies may allow one to define physiological tumor subvolumes consisting of areas of possible chronic hypoxia, areas of high perfusion, areas of high diffusion, and areas containing high choline concentrations. These physiological tumor subvolumes could be selectively boosted to increase local control of malignant brain tumors once one has determined which of these physiological tumor subvolumes predicts for local tumor recurrence after conventional radiotherapy.

In this technique a user assisted automatic registration technique is used that is based on an analytical estimate for the transformation matrix needed to register two rigid bodies. The only user input needed is three non-collinear points selected based on landmarks in the primary image and the corresponding three points in the secondary image. Since this registration technique uses two sets of at least three user-defined landmark points each of which has some selection error associated with it, the final registration will have an error that depends only on the selection error associated with the point sets.

Since physiological image studies are acquired at the same setting as the T1- w MRI their spatial orientation with respect to the T1- w MRI is known. Therefore, the registration of multiple physiological image studies to the treatment planning CT can be accomplished by first correlating them to the T1- w MRI, and in a second step the T1- w MRI is then registered to the treatment planning CT. The desired registration of the physiological image studies to the treatment planning CT is then accomplished by simply composing the appropriate transformation matrices.
Stereotactic Radiosurgery for Brain Tumors in Pediatric Patients
Authors: Suh John H. , Barnett Gene H.
Published: October 2014

Brain tumors represent the most common solid tumor in children. Fractionated radiation therapy has been an important treatment modality in the multi-disciplinary management of these tumors. Stereotactic radiosurgery is the precise delivery of a single fraction of radiation and has been an important treatment option for adult brain tumor patients. Although the use of stereotactic radiosurgery in pediatric brain tumors is much less frequent, it represents an important alternative for patients with recurrent, surgically inaccessible or radioresponsive tumors. This article will review the results and logistical issues of this modality in the management of pediatric brain tumors.
Boron Neutron Capture Therapy: Cellular Targeting of High Linear Energy Transfer Radiation
Authors: Coderre Jeffrey A. , Turcotte Julie C. , Riley Kent J. , Binns Peter J. , Harling Otto K. , Kiger W. S.
Published: October 2014

Boron neutron capture therapy (BNCT) is based on the preferential targeting of tumor cells with10 B and subsequent activation with thermal neutrons to produce a highly localized radiation. In theory, it is possible to selectively irradiate a tumor and the associated infiltrating tumor cells with large single doses of high-LET radiation while sparing the adjacent normal tissues. The mixture of high- and low-LET dose components created in tissue during neutron irradiation complicates the radiobiology of BNCT. Much of the complexity has been unravelled through a combination of preclinical experimentation and clinical dose escalation experience. Over 350 patients have been treated in a number of different facilities worldwide. The accumulated clinical experience has demonstrated that BNCT can be delivered safely but is still defining the limits of normal brain tolerance. Several independent BNCT clinical protocols have demonstrated that BNCT can produce median survivals in patients with glioblastoma that appear to be equivalent to conventional photon therapy. This review describes the individual components and methodologies required for effect BNCT: the boron delivery agents; the analytical techniques; the neutron beams; the dosimetry and radiation biology measurements; and how these components have been integrated into a series of clinical studies. The single greatest weakness of BNCT at the present time is non-uniform delivery of boron into all tumor cells. Future improvements in BNCT effectiveness will come from improved boron delivery agents, improved boron administration protocols, or through combination of BNCT with other modalites.
Optimization of Physical Dose Distributions with Hadron Beams: Comparing Photon IMRT with IMPT
Authors: Oelfke U. , Bortfeld T.
Published: October 2014

Intensity modulated radiotherapy with high enengy photons (IMRT) and with charged particles (IMPT) refer to the most advanced development in conformal radiation therapy. Their general aim is to increase local tumor control rates while keeping the radiation induced complications below desired thresholds. IMRT is currently widely introduced in clinical practice. However, the more complicated IMPT is still under development. Especially, spot-scanning techniques integrated in rotating gantries that can deliver proton or light ion-beams to a radiation target from any direction will be available in the near future.

We describe the basic concepts of intensity modulated particle therapy (IMPT). Starting from the potential advantages of hadron therapy inverse treatment planning strategies are discussed for various dose delivery techniques of IMPT. Of special interest are the techniques of distal edge tracking (DET) and 3D-scanning. After the introduction of these concepts a study of comparative inverse treatment planning is presented. The study aims to identify the potential advantages of achievable physical dose distributions with proton and carbon beams, if different dose delivery techniques are employed. Moreover, a comparison to standard photon IMRT is performed.

The results of the study are summarized as: i) IMRT with photon beams is a strong competitor to intensity modulated radiotherapy with charged particles. The most obvious benefit observed for charged particles is the reduction of medium and low doses in organs at risk. ii) The 3D-scanning technique could not improve the dosimetric results achieved with DET, although 10–15 times more beam spots were employed for 3D-scanning than for DET. However, concerns may arise about the application of DET, if positioning errors of the patient or organ movements have to be accounted for. iii) Replacing protons with carbon ions leads to further improvements of the physical dose distributions. However, the additional degree of improvement due to carbon ions is modest. The main clinical potential of heavy ion beams is probably related to their radiobiological properties.
Range, Range Modulation, and Field Radius Requirements for Proton Therapy of Prostate Cancer
Authors: Moyers M. F. , Miller D. W.
Published: October 2014

The Loma Linda University Proton Treatment Facility has treated over 5,000 patients for prostate cancer. Other institutions may find information regarding field size and range requirements for this population of patients useful for designing new proton beamlines. The maximum range, range modulation, and maximum field radius for 240 fields of prostate patients undergoing treatment were sampled and analyzed. Most fields required a range less than 290 mm of water, a modulation width less than or equal to 120 mm, and a radius less than 75 mm.
Comparison of Water and Lipid Content Measurements Using Diffuse Optical Spectroscopy and MRI in Emulsion Phantoms
Authors: Merritt Sean , Gulsen Gultekin , Chiou George , Chu Yong , Deng Chengwu , Cerussi Albert E. , Durkin Anthony J. , Tromberg Bruce J , Nalcioglu Orhan
Published: October 2014

We present a quantitative comparison of lipid and water signals obtained from broadband Diffuse Optical Spectroscopy (DOS) and Magnetic Resonance Imaging (MRI). DOS and MRI measurements were performed on an identical set of emulsion phantoms that were composed of different water/soybean oil fractions. Absolute concentrations of water and lipid ranging from 35–94% and 63–6%, respectively were calculated from quantitative broadband near-infrared (NIR) absorption spectra (650–1000 nm). MR images of fat and water were separated using the three-point Dixon technique. DOS and MRI measured water and lipid were highly correlated (R2 = 0.98 and R2 = 0.99, respectively) suggesting that these techniques are complementary over a broad range of physiologically relevant water and lipid values. In addition, comparison of DOS derived concentrations to the MRI “gold standard” technique validates our quantitation approach and permits estimation of DOS accuracy and sensitivity in vivo.
The Imaging of Apoptosis with the Radiolabeled annexin V: Optimal Timing for Clinical Feasibility
Authors: Belhocine Tarik , Steinmetz Neil , Li Chun , Green Allan , Blankenberg Francis G
Published: October 2014

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.
Stereotactic Radiosurgery versus Fractionated Stereotactic Radiotherapy Boost for Patients with Glioblastoma Multiforme
Authors: Cho Kwan H. , Hall Walter A. , Lo Simon S. , Dusenbery Kathryn E.
Published: October 2014

The aim of this study is to evaluate the efficacy of stereotactic radiotherapy boost (SRB) in patients with glioblastoma multiforme (GBM) by comparing two different regimens, single dose or fractionated treatment. Between December 1994 and January 2000, 24 patients with GBM were treated with SRB in conjunction with external beam radiotherapy (EBRT). Fourteen patients (58%) were treated with stereotactic radiosurgery (SRS) and 10 patients (42%) with fractionated stereotactic radiotherapy (FSRT). Median interval between EBRT and SRS or FSRT was 1.4 months (range −0.4–3.9 months). Actuarial survival rates of the entire 24 patients at one and two years following SRB were 63% and 34% respectively, with median survival time of 16 months. Variables predicting survival were age, extent of surgery, re-operation and the RTOG (Radiation Therapy Oncology Group) classes based on recursive partitioning analysis (RPA). In comparison to historical controls, improved survival benefit after SRB was observed. The median survival times for the RTOG classes 4, 5, and 6 were 28.3, 10.3, and 6.0 months following EBRT+SRB, respectively. Expected values for these classes after EBRT are 11.1, 8.9, and 4.6 months, respectively. This improvement in survival was seen predominantly for the RTOG class 4. There was no difference in survival between SRS and FSRT treated groups. Late complications developed in 4 patients in the SRS group and 1 patients in the FSRT group. Our retrospective data suggest that SRB in conjunction with EBRT may improve survival in patients with GBM with median survival time of 16 months, when compared to historical controls of the RTOG data following EBRT. The addition of SRB appeared to improve the median survival most demonstrably in RTOG RPA class 4 patients. SRS and FSRT are equally effective with similar median survival, but potentially less late complications associated with FSRT. Since this is a nonrandomized study, further investigation is needed to confirm this and to determine an optimal dose/fractionation scheme.
Improved Display of Synthetic IgG-Binding Domains on the Baculovirus Surface
Authors: Ojala Kirsi , Koski Johanna , Ernst Wolfgang , Grabherr Reingard , Jones Ian , Oker-Blom Christian
Published: October 2014

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.
Laparoscopic Cryotherapy for Renal Tumors
Authors: Spaliviero Massimiliano , Moinzadeh Alireza , Gill Inderbir S.
Published: October 2014

In an effort to decrease operative morbidity, energy based ablative procedures have triggered considerable interest in the treatment of select, small (<3 cm) renal tumors. Renal cryoablation for small renal tumors is a well-studied energy based ablative procedure that shows considerable promise as an alternative to partial nephrectomy. Cryoablation is minimally invasive and has demonstrated acceptable intermediate-term results. In this article we review key laboratory research and current clinical series of renal cryoablation.
Cryosurgery for Tumors — A Clinical Overview
Authors: Gage Andrew A. , Baust John G.
Published: October 2014

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.
HDR Brachytherapy with Surface Applicators: Technical Considerations and Dosimetry
Authors: Sabbas Albert M. , Kulidzhanov Fridon G. , Presser Joseph , Hayes Mary K. , Nori Dattatreyudu
Published: October 2014

HDR surface molds offer an alternative radiotherapy modality to electrons for the treatment of skin lesions. Treatment planning and dosimetry are discussed for two types of surface molds used in our clinic. Standard rectangular applicators are used on a variety of sites where surface curvature is minimal. In these cases an idealized planar geometry is used for treatment planning dose calculations. The calculations yield treatment dose uniformity at the prescription depth in tissue as well as skin dose, as a percentage of the treatment dose, and its dose uniformity. The availability of optimization techniques results in superior dose uniformity at depth but the dose at the skin has to be carefully evaluated. We have studied the dependence of these dosimetric parameters on the size of the surface mold and the type of optimization procedure used in the dosimetry calculations. The second type of surface applicator involves the use of a customized silicone rubber mold attached to a thermoplastic mask of the patient. We have used them to treat lesions of the face where surface curvatures are appreciable and reproducibility of setup is more critical. In these cases a CT data set is used for reconstruction of the catheters, activation of relevant dwell positions and dosimetry, including optimization. Towards establishing effective methods for quality assurance of the optimized HDR surface mold planning calculations, we have compared their dosimetry to both a classical brachytherapy system and to one based on an analytical model of the applicator. The classical system yields an independent verification of the integrated activity used in the planning calculations, whereas the analytical model is used to evaluate depth dose dependence on mold size and optimization.
Near Infrared Spectroscopy and Imaging to Probe Differences in Water Content in Normal and Cancer Human Prostate Tissues
Authors: Ali J. H. , Wang W. B. , Zevallos M. , Alfano R. R.
Published: October 2014

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 700nm, 800nm, 1200nm, and 1450nm 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 H2O molecules in the NIR.
Determination of Grade and Receptor Status from the Primary Breast Lesion by Magnetic Resonance Spectroscopy
Authors: Lean Cynthia , Doran Sinead , Somorjai Ray L. , Malycha Peter , Clarke David , Himmelreich Uwe , Bourne Roger , Dolenko Brion , Nikulin Alexander E. , Mountford Carolyn
Published: October 2014

Magnetic resonance spectra (MRS) from fine needle aspiration biopsies (FNAB) from primary breast lesions were analysed using a pattern recognition method, Statistical Classification Strategy, to assess tumor grade and oestrogen receptor (ER) and progesterone receptor (PgR) status. Grade 1 and 2 breast cancers were separated from grade 3 cancers with a sensitivity and specificity of 96% and 95%, respectively. The ER status was predicted with a sensitivity of 91% and a specificity of 90%, and the PgR status with a sensitivity of 91% and a specificity of 86%. These classifiers provide rapid and reliable, computerized information and may offer an objective method for determining these prognostic indicators simultaneously with the diagnosis of primary pathology and lymph node involvement.
Quantitative Pathology in Tissue MR Spectroscopy Based Human Prostate Metabolomics
Authors: Burns Melissa A. , He Wenlei , Wu Chin-Lee , Cheng Leo L.
Published: October 2014

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 pathological findings. Because metabolomics is a quantitative study, its clinical value can be rigorously investigated by determining its association with other quantitative measures. The human visual assessment of prostate tissue, however, introduces both inter- and intra-observer biases that may limit the reliability of its quantitations, and therefore, the strength of its correlations with metabolomic profiles. The aim of this study was to develop a simple, feasible protocol for the computer-aided image analysis (CAIA) of prostate pathology slides in order to achieve quantitative pathology from tissue samples, following metabolomic measurement with high-resolution magic angle spinning (HRMAS) magnetic resonance spectroscopy (MRS). Thirty-eight samples from 29 prostatectomy cases were studied with HRMAS MRS. After spectroscopy analysis, samples were serial-sectioned, stained and visually assessed by pathologists. Cross-sections from these samples were then measured with the CAIA protocol. Results showed a two-fold difference between human visual assessments of the area percentages of tissue pathologies and CAIA area percentages obtained for the same features. Linear correlations were found between both metabolites indicative of normal epithelium and those indicative of prostate cancer, and the CAIA quantitative results. CAIA based quantitative pathology is more reliable than human visual assessment in establishing correlations useful for disease diagnosis between prostate pathology and metabolite concentrations.
Helical Tomotherapy as a Means of Delivering Accelerated Partial Breast Irradiation
Authors: Hui Susanta K. , Das Rupak K. , Kapatoes Jeff , Oliviera Gustavo , Becker Stuart , Odau Heath , Fenwick John D. , Patel Rakesh , Kuske Robert , Mehta Minesh , Paliwal Bhudatt , Mackie Thomas R. , Fowler Jack F. , Welsh James S.
Published: October 2014

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 C T. 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” (≥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.
Radiosensitization of Murine Ehrlich Ascites Tumor by a Combination of 2-deoxy-D-Glucose and 6-Aminonicotinamide
Authors: Varshney R , Gupta S , Dwarakanath B S
Published: October 2014

Enhanced radiosensitizing effects of a combination of 2-deoxy-D-glucose (2-DG), a glycolytic inhibitor and 6-aminonicotinamide (6-AN) an analogue of nicotinamide, which inhibits hexose monophosphate shunt (HMP) have been demonstrated in vitro. The purpose of the present studies is to investigate in vivo effects of this combination in Ehrlich ascites tumor (EAT) bearing mice. EAT tumor was grown in Swiss albino strain A mice. Treatment induced growth delay and tumor free animal survival were evaluated as parameters of radiation response. Focal irradiation of the tumor with a single fraction of 10 Gy induced a moderate delay in tumor growth but did not lead to complete regression of the tumor. Intravenous administration of either 6-AN or 2-DG immediately before irradiation enhanced radiation-induced growth delay with a cure rate of 45%. However, administration of a combination of 2-DG (2 g/kg b.wt.) and 6-AN (2 mg/kg b.wt.) immediately before irradiation led to complete regression of tumor in 80% animals resulting in survival of more than 300 days. A similar response (≈80%) was observed when 2-DG dose was reduced to 1 g/kg in combination with 6-AN. It is concluded that 6-AN enhances the radiosensitizing effects of 2-DG and the combination may have potential application in improving radiotherapy of tumors.
Issues in Breast Cancer Screening
Authors: Pisano Etta
Published: October 2014

This paper will review the use of screening mammography in the United States, with an emphasis on its limitations as currently practiced. It will then emphasize several areas where breast cancer imaging practice can be improved, namely in reducing overtreatment of potentially nonlethal cancers, in monitoring the effectiveness of nonsurgical therapies, and in guiding noninvasive therapies. Any new modality that is to have an impact on breast cancer mortality must perform comparably to screening mammography to become widely utilized. While mammography is not perfect, it has set a high threshold that other modalities must reach before they will be widely utilized for screening or diagnosis.
Positron Emission Mammography: High-Resolution Biochemical Breast Imaging
Authors: Weinberg Irving N. , Beylin David , Zavarzin Valera , Yarnall Steve , Stepanov Pavel Y. , Anashkin Edward , Narayanan Deepa , Dolinsky Sergei , Lauckner Kathrin , Adler Lee P.
Published: October 2014

Positron emission mammography (PEM) provides images of biochemical activity in the breast with spatial resolution matching individual ducts (1.5 mm full-width at half-maximum). This spatial resolution, supported by count efficiency that results in high signal-to-noise ratio, allows confident visualization of intraductal as well as invasive breast cancers. Clinical trials with a full-breast PEM device have shown high clinical accuracy in characterizing lesions identified as suspicious on the basis of conventional imaging or physical examination (sensitivity 93%, specificity 83%, area under the ROC curve of 0.93), with high sensitivity preserved (91%) for intraductal cancers. Increased sensitivity did not come at a cost of reduced specificity. Considering that intraductal cancer represents more than 30% of reported cancers, and is the form of cancer with the highest probability of achieving surgical cure, it is likely that the use of PEM will complement anatomic imaging modalities in the areas of surgical planning, high-risk monitoring, and minimally invasive therapy. The quantitative nature of PET promises to assist researchers interested studying the response of putative cancer precursors ( e.g., atypical ductal hyperplasia) to candidate prevention agents.
An Amorphous Selenium Based Positron Emission Mammography Camera with Avalanche Gain
Authors: Reznik A. , Lui B. J. M. , Rowlands J. A.
Published: October 2014

Early diagnosis of breast cancer is crucial for effective treatment, and the need exists for greater detection ability and specificity than possible by screening x-ray mammography (currently the primary imaging technique for the detection of breast lesions). Positron Emission Tomography (PET) using the radiotracer 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) offers a noninvasive, highly sensitive method for the diagnosis of breast cancer. Images from PET contain unique metabolic information that is not available from anatomical imaging techniques. We propose a Positron Emission Mammography (PEM) imaging system that maintains the established high specificity of FDG PET while providing improved collection efficiency for the radiotracer signal and the potential for images with better spatial resolution. This PEM system will enable detection of lesions that are considerably smaller than those that can be visualized using whole body PET imaging.

The compact dual-head PEM camera will be based on an amorphous selenium (a-Se) avalanche photodetector and the scintillator lutetium oxyorthosilicate (LSO). The camera promises high collection efficiency by combining the fast scintillation light decay and high light yield of LSO with the excellent quantum efficiency, large avalanche gain, and rapid response time of a-Se. We have measured the gain and readout time of an 8 μm a-Se layer and demonstrated the feasibility of the proposed PEM camera.
Microwave Imaging of the Breast
Authors: Fear Elise C.
Published: October 2014

Microwave imaging for medical applications has been of interest for many years. Recently, microwave imaging for breast cancer detection has gained attention due to advances in imaging algorithms, microwave hardware and computational power. The breast is relatively translucent to microwaves, accessible for imaging, and there appears to be a significant electromagnetic property contrast between tumors and healthy tissues. Therefore, breast imaging may be the first clinically viable application of microwave imaging. This paper reviews recent developments in passive, hybrid, and active approaches to microwave breast cancer detection.
Potential Applications of Vibro-acoustography in Breast Imaging
Authors: Alizad Azra , Whaley Dana H. , Greenleaf James F. , Fatemi Mostafa
Published: October 2014

Vibro-acoustography has gained interest in the recent years as a new modality for medical imaging. This method is based on low-frequency vibrations induced in the object by the radiation force of ultrasound. This paper focuses on potential applications of vibro-acoustography in breast imaging, including detection of microcalcifications, detection of arterial calcifications, and soft tissue imaging. In addition, we will briefly discuss our recent results of in vivo breast vibro-acoustography. Future developments and potential impact of vibro-acoustography in breast imaging are also discussed.
Optical Tomography with Ultrasound Localization: Initial Clinical Results and Technical Challenges
Authors: Zhu Quing
Published: October 2014

Optical tomography with ultrasound localization utilizes co-registered ultrasound lesion structure information to guide optical imaging reconstruction. A hand-held probe consisting of a commercial ultrasound transducer and near infrared optical imaging sensors was used to simultaneously acquire ultrasound images and optical measurements. A dual-mesh scheme was used to map the ultrasound-visible lesions to finer-grid lesion regions and coarser-grid background regions for optical imaging reconstruction. As a result, optical imaging reconstruction was well-conditioned for inverse mapping of lesion hemoglobin concentration and blood oxygen saturation. Initial clinical results have shown that early stage invasive cancers may be distinguished by a two-fold greater total hemoglobin concentration compared with fibroadenomas and other benign lesions. Initial results of advanced cancers have shown that the hemoglobin distribution is highly distorted and heterogeneous and the distorted distributions correlate with histological microvessel density counts and could be used to assess chemotherapy response.
Spectral and Temporal Near-Infrared Imaging of Ex Vivo Cancerous and Normal Human Breast Tissues
Authors: Alrubaiee M. , Gayen S. K. , Alfano R. R. , Koutcher J. A.
Published: October 2014

Cancerous and normal ex vivo human breast tissues were investigated using spectroscopic and time-sliced two-dimensional (2- D) transillumination imaging methods in order to demonstrate the importance and potential of spectral and temporal measurements in breast cancer detection and diagnosis. The experimental arrangement for time-sliced optical imaging used 120 fs, 1 kHz repetition-rate, 800 nm light pulses from a Ti:sapphire laser system for sample illumination, and a 80 ps resolution ultrafast gated intensified camera system for recording 2- D time-sliced images. The spectroscopic imaging arrangement used 1225–1300 nm tunable output of a Cr: forsterite laser for sample illumination, a Fourier space gate to discriminate against multiple-scattered light, and a near-infrared area camera to record 2- D images. Images recorded with earlier temporal slices of transmitted light highlighted tumors, while those recorded with later slices accentuated normal tissues. When light was tuned closer to the 1203 nm absorption resonance of adipose tissues, a marked enhancement in contrast between the images of adipose and fibrous tissues was observed. A similar wavelength-dependent difference between normal and cancerous tissues was observed. These results correlate well with pathology and nuclear magnetic resonance based analyses of the samples.
The Molecular Analysis of Breast Cancer Utilizing Targeted Nanoparticle Based Ultrasound Contrast Agents
Authors: Sakamoto Jason H. , Smith Bryan R. , Xie Bin , Rokhlin Stanislav I. , Lee Stephen C. , Ferrari Mauro
Published: October 2014

This study was structured to challenge the hypothesis that nano-sized particulates could be molecularly targeted and bound to the prognostic and predictive HER-2/neu cell membrane receptor to elicit detectable changes in ultrasound response from human breast cancer cells. SKBR-3 human breast cancer cells were enlisted to test the efficacy of the particle conjugation strategy used in this study and ultimately, to provide conclusive remarks regarding the validity of the stated hypothesis. A characterization-mode ultrasound (CMUS) system was used to apply a continuum mechanics based, two-step inversion algorithm to reconstruct the mechanical material properties of four cell/agarose test conditions upon three independent test samples. The four test conditions include: Herceptin® conjugated iron oxide nanoparticles bound to cells (HER-con), Herceptin® bound to cells (HER), iso-type matched antibody conjugated iron oxide nanoparticles bound to cells (ISO-con), and Cold Flow Buffer mixed with agarose (CFB). The statistical analysis of these ultrasound results supported the ability to differentiate between HER-2/neu positive SKBR-3 cells that have been successfully tagged with Herceptin® conjugated iron oxide particles to those that have not demonstrated particle binding. These findings serve as promising proof-of-concept data for the development of a quantitative histopathologic evaluation tool directed towards both in situ and in vivo applications. The ultimate goal of this research is to exploit the molecular expression of the HER-2/neu protein to offer rapid, quantitative ultrasound information concerning the malignancy rating of human breast tissue employing tumor targeting nanoparticle based ultrasound contrast agents. When fully developed, this could potentially help 32,000–63,000 women efficiently find their proper treatment strategy to fight and win their battle against breast cancer.
Implementation of Talairach Atlas Based Automated Brain Segmentation for Radiation Therapy Dosimetry
Authors: Popple Richard A. , Griffith H. Randall , Sawrie Stephen M. , Fiveash John B. , Brezovich Ivan A.
Published: October 2014

Radiotherapy for brain cancer inevitably results in irradiation of uninvolved brain. While it has been demonstrated that irradiation of the brain can result in cognitive deficits, dose-volume relationships are not well established. There is little work correlating a particular cognitive deficit with dose received by the region of the brain responsible for the specific cognitive function. One obstacle to such studies is that identification of brain anatomy is both labor intensive and dependent on the individual performing the segmentation. Automatic segmentation has the potential to be both efficient and consistent. Brains2 is a software package developed by the University of Iowa for MRI volumetric studies. It utilizes MR images, the Talairach atlas, and an artificial neural network (ANN) to segment brain images into substructures in a standardized manner. We have developed a software package, Brains2DICOM, that converts the regions of interest identified by Brains2 into a DICOM radiotherapy structure set. The structure set can be imported into a treatment planning system for dosimetry. We demonstrated the utility of Brains2DICOM using a test case, a 34-year-old man with diffuse astrocytoma treated with three-dimensional conformal radiotherapy. Brains2 successfully applied the Talairach atlas to identify the right and left frontal, parietal, temporal, occipital, subcortical, and cerebellum regions. Brains2 was not successful in applying the ANN to identify small structures, such as the hippocampus and caudate. Further work is necessary to revise the ANN or to develop new methods for identification of small structures in the presence of disease and radiation induced changes. The segmented regions-of-interest were transferred to our commercial treatment planning system using DICOM and dose-volume histograms were constructed. This method will facilitate the acquisition of data necessary for the development of normal tissue complication probability (NTCP) models that assess the probability of cognitive complications secondary to radiotherapy for intracranial and head and neck neoplasms.