bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroprotective strategies in drug abuse‐evoked encephalopathy
Authors: Virmani Ashraf , Ali Syed F. , Binienda Zbigniew K.
Published: April 2010

Encephalopathy is evidenced as an altered mental state with various neurological symptoms, such as memory and cognitive problems. The type of a substance‐evoked encephalopathy will depend on the drug, substance, or combination being abused. The categories into which we could place the various abused substances could be tentatively divided into stimulants, amphetamines, hallucinogens, narcotics, inhalants, anesthetics, anabolic steroids, and antipsychotics/antidepressants. Other factors that may underlie encephalopathy, such as infectious agents, environmental, and other factors have also to be taken into account. Drugs of abuse can be highly toxic to the CNS following acute, but more so in chronic exposure, and can produce significant damage to other organs, such as the heart, lungs, liver, and kidneys. The damage to these organs may be at least partially reversible when drug abuse is stopped but CNS damage from repeated or prolonged abuse is often irreversible. The major pathways for the organ and CNS toxicity could be related to ischemic events as well as increased cell damage due to metabolic or mitochondrial dysfunction resulting in increased excitotoxicity, reduced energy production, and lowered antioxidant potential. These susceptibilities could be strengthened by the use of antioxidants to combat free radicals (e.g., vitamin E, lipoic acid); trying to improve energy generation by using mitochondriotropic/metabolic compounds (e.g., thiamine, coenzyme Q10, carnitine, riboflavin); by reducing excitotoxicity (e.g., glutamate antagonists) and other possible strategies, such as robust gene response, need to be investigated further. The drug‐abuse‐evoked encephalopathy still needs to be studied further to enable better preventative and protective strategies.
Isoflurane modulates neuronal excitability of the nucleus reticularis thalami in vitro
Authors: Joksovic Pavle M. , Todorovic Slobodan M.
Published: April 2010

The thalamus has a key function in processing sensory information, sleep, and cognition. We examined the effects of a common volatile anesthetic, isoflurane, on modulation of neuronal excitability in reticular thalamic nucleus (nRT) in intact brain slices from immature rats. In current‐clamp recordings, isoflurane (300–600 μmol/L) consistently depolarized membrane potential, decreased input resistance, and inhibited both rebound burst firing and tonic spike firing modes of nRT neurons. The isoflurane‐induced depolarization persisted not only in the presence of tetrodotoxin, but after replacement of Ca2+ with Ba2+ ions in external solution; it was abolished by partial replacement of extracellular Na+ ions with N‐methyl‐D‐glucamine. In voltage‐clamp recordings, we found that isoflurane slowed recovery from inactivation of T‐type Ca2+ current. Thus, at clinically relevant concentrations, isoflurane inhibits neuronal excitability of nRT neurons in developing brain via multiple ion channels. Inhibition of the neuronal excitability of thalamic cells may contribute to impairment of sensory information transfer in the thalamocortical network by general anesthetics. The findings may be important for understanding cellular mechanisms of anesthesia, such as loss of consciousness and potentially damaging consequences of general anesthetics on developing mammalian brains.
Acetyl‐l‐carnitine reduces the infarct size and striatal glutamate outflow following focal cerebral ischemia in rats
Authors: Jalal Fakhreya Yousuf , Böhlke Mark , Maher Timothy J.
Published: April 2010

Acetyl‐l‐carnitine (ALCAR), an endogenous water soluble molecule, is synthesized in the brain and is involved in many aspects of neuronal activity, including metabolism and neuronal membrane formation and integrity. To determine ALCAR's neuroprotective effects, focal cerebral ischemia was induced using four models of middle cerebral artery occlusion (MCAO) and treatment with 0–400 mg/kg ALCAR (i.p.) prior to MCAO. While acute doses were without effect, pretreatment with chronic ALCAR (400 mg/kg/day for five days) significantly reduced infarct size. Lower chronic ALCAR doses were not effective. Additionally, elevations in microdialysate glutamate post‐MCAO were attenuated by ALCAR treatment.
Metabolic syndrome, age‐associated neuroendocrine disorders, and dysregulation of tryptophan—kynurenine metabolism
Authors: Oxenkrug Gregory F.
Published: April 2010

The neuroendocrine theory of aging identified a cluster of conditions (hypertension, obesity, dyslipidemia, diabetes type 2, menopause, late onset depression, vascular cognitive impairment, impairment of immune defense, and some forms of cancer, e.g., breast and prostate) as age‐associated neuroendocrine disorders (AAND). Obesity, dyslipidemia, hypertension, and type 2 diabetes were later described as metabolic syndromes (MetS). Chronic inflammation is currently considered as a common feature of MetS/AAND. One of the mechanisms by which chronic inflammation might trigger and/or maintain the development of MetS/AAND is transcriptional induction of indoleamine 2,3‐dioxygenase (IDO), rate‐limiting enzyme of tryptophan (TRY)–kynurenine (KYN) pathway, by pro‐inflammatory cytokines (PIC). Activation of IDO shifts TRY metabolism from serotonin synthesis to formation of “kynurenines.” Diminished serotonin production is associated with mental depression while increased formation of kynurenines might contribute to development of MetS/AAND via their apoptotic, neurotoxic, and pro‐oxidative effects, and upregulation of inducible nitric oxide synthase, phospholipase A2, arachidonic acid, prostaglandin, 5‐lipoxygenase, and leukotriene cascade. The combined presence of high producers of alleles of polymorphic PIC genes (e.g., interferon‐gamma and tumor necrosis factor alpha) might account for the genetic predisposition to high levels of PIC production, leading to “superinduction” of IDO. The other rate‐limiting enzyme of the TRY–KYN pathway, TRY 2,3‐dioxygenase, is activated by substrate (TRY) and cortisol. Therefore, KYN–TRY metabolism might be the meeting point for gene‐environment interaction and a new target for prevention and treatment of MetS/AAND.
Neuroprotective efficacy of estrogen in experimental spinal cord injury in rats
Authors: Samantaray Supriti , Sribnick Eric A. , Das Arabinda , Thakore Nakul P. , Matzelle Denise , Yu Shan P. , Ray Swapan K. , Wei Ling , Banik Naren L.
Published: April 2010

Spinal cord injury (SCI) leads to neurological deficits and motor dysfunction. Methylprednisolone, the only drug used for treating SCI, renders limited neuroprotection and remains controversial. Estrogen is one of the most potent multiactive neuroprotective agents and it is currently under investigation in our laboratory for its efficacy in SCI. The present review briefly summarizes our earlier findings on the therapeutic potential of pharmacological/supraphysiological levels of estrogen in SCI and outlines our ongoing research, highlighting the efficacy of physiological levels of estrogen against neuronal injury, axonal degeneration, and gliosis and also the molecular mechanisms of such neuroprotection in experimental SCI. Furthermore, our ongoing studies designed to explore the different translational potential of estrogen therapy suggest that this multiactive steroid may act as an adjunct therapy to promote angiogenesis, thus enhancing the functional recovery following chronic SCI. Taken together, these studies confirm that estrogen is a potential therapeutic agent for treating SCI.
Statins and neuroprotection
Authors: Wood W. Gibson , Eckert Gunter P. , Igbavboa Urule , Müller Walter E.
Published: April 2010

There is growing interest in the use of statins, HMG‐CoA reductase inhibitors, for treating specific neurodegenerative diseases (e.g., cerebrovascular disease, Parkinson's disease, Alzheimer's disease, multiple sclerosis) and possibly traumatic brain injury. Neither is there a consensus on the efficacy of statins in treating the aforementioned diseases nor are the mechanisms of the purported statin‐induced neuroprotection well‐understood. Part of the support for statin‐induced neuroprotection comes from studies using animal models and cell culture. Important information has resulted from that work but there continues to be a lack of progress on basic issues pertaining to statins and brain that impedes advancement in understanding how statins alter brain function. For example, there are scant data on the pharmacokinetics of lipophilic and hydrophilic statins in brain, statin‐induced neuroprotection versus cell death, and statins and brain isoprenoids. The purpose of this mini‐review will be to examine those aforementioned issues and to identify directions of future research.
Physiological low dose of estrogen‐protected neurons in experimental spinal cord injury
Authors: Samantaray Supriti , Matzelle Denise D. , Ray Swapan K. , Banik Naren L.
Published: April 2010

A protective role for estrogen against neurodegeneration and neurotrauma has received enormous attention in recent years, unraveling multiple facets and thus establishing this steroid as a multiactive neuroprotectant. The present study briefly reports our findings on the neuroprotective efficacy of physiologically relevant low doses of estrogen in experimental spinal cord injury (SCI) in rats. The current finding further corroborates our earlier results on efficacy of pharmacological/supraphysiological levels of estrogen in SCI and adds to the significance of conducting preclinical studies on estrogen efficacy in SCI.
Nanotechnology applications and approaches for neuroregeneration and drug delivery to the central nervous system
Authors: Silva Gabriel A.
Published: April 2010

Nanotechnology is the science and engineering concerned with the design, synthesis, and characterization of materials and devices that have a functional organization in at least one dimension on the nanometer (i.e., one billionth of a meter) scale. The potential impact of bottom up self‐assembling nanotechnology, custom made molecules that self‐assemble or self‐organize into higher ordered structures in response to a defined chemical or physical cue, and top down lithographic type technologies where detail is engineered at smaller scales starting from bulk materials, stems from the fact that these nanoengineered materials and devices exhibit emergent mesocale and macroscale chemical and physical properties that are often different than their constituent nanoscale building block molecules or materials. As such, applications of nanotechnology to medicine and biology allow the interaction and integration of cells and tissues with nanoengineered substrates at a molecular (i.e., subcellular) level with a very high degree of functional specificity and control. This review considers applications of nanotechnology aimed at the neuroprotection and functional regeneration of the central nervous system (CNS) following traumatic or degenerative insults, and nanotechnology approaches for delivering drugs and other small molecules across the blood‐brain barrier. It also discusses developing platform technologies that may prove to have broad applications to medicine and physiology, including some being developed for rescuing or replacing anatomical and/or functional CNS structures.
Neuromodulation
Authors: Andrews Russell J.
Published: April 2010

Many nervous system disorders (e.g., Parkinson's disease, mood disorders) involve neurotransmitters as well as electrical activity. Pharmacologic treatment does not target the precise location(s) where neurotransmitter imbalances occur. Additionally, non‐neuronal cells in the brain—notably astrocytes—influence neuronal activity through both electrical and neurochemical modulation of nearby neurons. Precise monitoring/recording and modulating/stimulating (both electrical and neurochemical) can optimize therapy in specific disorders and specific patients. Carbon‐fiber microelectrodes (5 μm diameter) in freely moving rodents have shown that dopamine release is heterogeneous within various regions in the nucleus accumbens, a region involved in many mood disorders. Because neurons are only several microns in diameter (axons, dendrites, and synaptic clefts smaller still), ultramicroelectrodes will be essential to selectively monitor/modulate the cell body, the axon, or at the intracellular level. Nanoelectrode arrays can monitor both electrical activity and dopamine in real time with submicron resolution, and stimulate neurons with equal precision. Computational models indicate that precise monitoring/modulating (electrically and neurochemically) at the subnucleus or neuron level will be necessary to restore normal firing patterns and neurotransmitter levels in many brain disorders. Endovascular techniques can introduce ultramicroelectrodes (0.5 micron or smaller) into the brain via capillaries; such electrodes can stimulate/record neuronal tissue with a response virtually identical to extra‐vascular microelectrodes. Within the next decade, hundreds if not thousands of submicron‐sized monitoring/modulating electrodes can be placed wherever needed to restore brain function to normal. The term “neuromodulation” will likely replace deep brain stimulation (DBS) as both neurochemistry and electrical activity are included in the therapeutic modalities.
Constrained Kalman Filtering: Additional Results
Authors: Pizzinga Adrian
Published: April 2010

This paper deals with linear state space modelling subject to general linear constraints on the state vector. The discussion concentrates on four topics: the constrained Kalman filtering versus the recursive restricted least squares estimator; a new proof of the constrained Kalman filtering under a conditional expectation framework; linear constraints under a reduced state space modelling; and state vector prediction under linear constraints. The techniques proposed are illustrated in two real problems. The first problem is related to investment analysis under a dynamic factor model, whereas the second is about making constrained predictions within a GDP benchmarking estimation.
Qualitative Research in the Service of Understanding Learners and Users of Statistics
Authors: Gal Iddo , Ograjenšek Irena
Published: April 2010

This paper seeks to add to a scholarly dialogue regarding the role and value of qualitative techniques in research on learning and using statistics. The paper briefly outlines some of the core assumptions of qualitative research methods, and presents four examples to illustrate selected qualitative methods that are used by educational researchers and service organizations. The discussion emphasizes the need to integrate quantitative and qualitative approaches in research on learners and users of statistics, and suggests that such integration may be needed to study emerging web‐based communities of learners and users of statistics.
PEAS V1.0: a package for elementary analysis of SNP data
Authors: XU SHUHUA , GUPTA SANCHIT , JIN LI
Published: April 2010

We have developed a software package named PEAS to facilitate analyses of large data sets of single nucleotide polymorphisms (SNPs) for population genetics and molecular phylogenetics studies. PEAS reads SNP data in various formats as input and is versatile in data formatting; using PEAS, it is easy to create input files for many popular packages, such as STRUCTURE, frappe, Arlequin, Haploview, LDhat, PLINK, EIGENSOFT, PHASE, fastPHASE, MEGA and PHYLIP. In addition, PEAS fills up several analysis gaps in currently available computer programs in population genetics and molecular phylogenetics. Notably, (i) It calculates genetic distance matrices with bootstrapping for both individuals and populations from genome‐wide high‐density SNP data, and the output can be streamlined to MEGA and PHYLIP programs for further processing; (ii) It calculates genetic distances from STRUCTURE output and generates MEGA file to reconstruct component trees; (iii) It provides tools to conduct haplotype sharing analysis for phylogenetic studies based on high‐density SNP data. To our knowledge, these analyses are not available in any other computer program. PEAS for Windows is freely available for academic users from http://www.picb.ac.cn/~xushua/index.files/Download_PEAS.htm.
ANCA‐positive vasculitis associated with simvastatin/ezetimibe: expanding the spectrum of statin‐induced autoimmunity?
Authors: SEN Deepali , ROSENSTEIN Elliot D. , KRAMER Neil
Published: April 2010

Although autoimmune syndromes such as systemic lupus erythematosus and dermatomyositis have been previously reported in association with statin use, vasculitis has not been well described. We present a patient with an antineutrophil cytoplasmic antibody‐positive, predominantly cutaneous vasculitis, the temporal course of which was associated with simvastatin/ezetimibe use. The patient’s serologic findings were consistent with drug‐induced disease, with high titer antimyeloperoxidase, in addition to antinuclear and anti‐Ro (SSA) antibodies. The patient demonstrated complete resolution of symptoms simply by withdrawing the drug.
The theta‐logistic is unreliable for modelling most census data
Authors: Clark Francis , Brook Barry W. , Delean Steven , Reşit Akçakaya H. , Bradshaw Corey J. A.
Published: April 2010

1.The theta‐logistic is a simple and flexible model for describing how the growth rate of a population slows as abundance increases. Starting atrm(taken as the maximum population growth rate), the growth response decreases in a convex or concave way (according to the shape parameter θ) to zero when the population reaches carrying capacity.

2.We demonstrate that fitting this model to census data is not robust and explain why. The parameters θ andrmare able to play‐off against each other (providing a constant product), thus allowing both to adopt extreme and ecologically implausible values.

3.We use simulated data to examine: (i) a population fluctuating around a constant carrying capacity (K); (ii) recovery of a population from 10% of carrying capacity; and (iii) a population subject to variation inK. We show that estimates of extinction risk depending on this or similar models are therefore prone to imprecision. We refute the claim that concave growth responses are shown to dominate in nature.

4.As the model can also be sensitive to temporal variation in carrying capacity, we argue that the assumption of a constant carrying capacity is both problematic and presents a fruitful direction for the development of phenomenological density‐feedback models.
Refraction corrected transmission ultrasound computed tomography for application in breast imaging
Authors: Li Shengying , Jackowski Marcel , Dione Donald P. , Varslot Trond , Staib Lawrence H. , Mueller Klaus
Published: April 2010

Purpose:

We present an iterative framework for CT reconstruction from transmission ultrasound data which accurately and efficiently models the strong refraction effects that occur in our target application: Imaging the female breast.

Methods:

Our refractive ray tracing framework has its foundation in the fast marching method (FNMM) and it allows an accurate as well as efficient modeling of curved rays. We also describe a novel regularization scheme that yields further significant reconstruction quality improvements. A final contribution is the development of a realistic anthropomorphic digital breast phantom based on the NIH Visible Female data set.

Results:

Our system is able to resolve very fine details even in the presence of significant noise, and it reconstructs both sound speed and attenuation data. Excellent correspondence with a traditional, but significantly more computationally expensive wave equation solver is achieved.

Conclusions:

Apart from the accurate modeling of curved rays, decisive factors have also been our regularization scheme and the high‐quality interpolation filter we have used. An added benefit of our framework is that it accelerates well on GPUs where we have shown that clinical 3D reconstruction speeds on the order of minutes are possible.
Measurement and modeling of the effect of support arm backscatter on dosimetry with a Varian EPID
Authors: Rowshanfarzad Pejman , McCurdy Boyd M. C. , Sabet Mahsheed , Lee Christopher , O'Connor Daryl J. , Greer Peter B.
Published: April 2010

Purpose:

Amorphous silicon EPIDs have been used for planar dose verification in IMRT treatments for many years. The support arm used to attach some types of EPIDs to linear accelerators can introduce inaccuracies to dosimetry measurements due to the presence of metallic parts in their structures. It is demonstrated that this uncertainty may be as large as of maximum image signal for large fields. In this study, a method has been described to quantify, model and correct for the effect of backscattered radiation from the EPID support arm (E‐Arm type, Varian Medical Systems).

Methods:

Measurements of a support arm backscatter kernel were made using several 6 MV pencil beam irradiations at a sample of positions over the sensitive area of the EPID in standard clinical setup and repeated with the EPID removed from the support arm but at the same positions. A curve‐fit to the subtraction of EPID response obtained on and off the arm was used to define the backscatter kernel. The measured kernel was compared with a backscatter kernel obtained by Monte Carlo simulations with EGS/BEAM code. A backscatter dose prediction using the measured backscatter kernel was added to an existing EPID dose prediction model. The improvement in the agreement of the modified model predictions with EPID measurements for a number of open fields and IMRT beams were investigated by comparison to the original model results.

Results:

Considering all functions tested to find the best functional fit to the data points, a broad Gaussian curve proved to be the optimum fit to the backscatter data. The best fit through the Monte Carlo simulated backscatter kernel was also found to be a Gaussian curve. The maximum decrease in normalized root mean squared deviation of the measured and modeled EPID image profiles for open fields was 13.7% for a field with no decrease observed for a (the smallest) field as it was not affected by the arm backscatter. Gamma evaluation (2%, 2 mm criteria) showed the improvement in agreement between the model and measurement results when the backscatter was incorporated. The average increase in Gamma pass rate was 2% for head and neck and 1.3% for prostate IMRT fields investigated in this study.

Conclusions:

The application of the backscatter kernel determined in this study improved the accuracy of dosimetry using a Varian EPID with E‐arm for open fields of different sizes: Eight head and neck and seven prostate IMRT fields. Further improvement in the agreement between the modelpredictions and EPID measurements requires more sophisticated modeling of the backscatter.
Adaptive spatial calibration of a 3D ultrasound system
Authors: Hartov Alex , Paulsen Keith , Ji Songbai , Fontaine Kathryn , Furon Marie‐Laure , Borsic Andrea , Roberts David
Published: April 2010

Purpose:

The authors present a method devised to calibrate the spatial relationship between a 3D ultrasound scanhead and its tracker completely automatically and reliably. The user interaction is limited to collecting ultrasound data on which the calibration is based.

Methods:

The method of calibration is based on images of a fixed plane of unknown location with respect to the 3D tracking system. This approach has, for advantage, to eliminate the measurement of the plane location as a source of error. The devised method is sufficiently general and adaptable to calibrate scanheads for 2D images and 3D volume sets using the same approach. The basic algorithm for both types of scanheads is the same and can be run unattended fully automatically once the data are collected. The approach was devised by seeking the simplest and most robust solutions for each of the steps required. These are the identification of the plane intersection within the images or volumes and the optimization method used to compute a calibration transformation matrix. The authors use adaptive algorithms in these two steps to eliminate data that would otherwise prevent the convergence of the procedure, which contributes to the robustness of the method.

Results:

The authors have run tests amounting to 57 runs of the calibration on two a scanhead that produce 3D imaging volumes, at all the available scales. The authors evaluated the system on two criteria: Robustness and accuracy. The program converged to useful values unattended for every one of the tests (100%). Its accuracy, based on the measured location of a reference plane, was estimated to be for all tests combined.

Conclusions:

The system presented is robust and allows unattended computations of the calibration parameters required for freehand tracked ultrasound based on either 2D or 3D imaging systems.
Measurement of ionization chamber absorbed dose factors in megavoltage photon beams
Authors: McEwen Malcolm R.
Published: April 2010

Purpose:

Absorbed dose beam quality conversion factors ( factors) were obtained for 27 different types of ionization chamber. The aim was to obtain objective evidence on the performance of a wide range of chambers currently available, and potentially used for reference dosimetry, and to investigate the accuracy of the calculation algorithm used in the TG‐51 protocol.

Methods:

Measurements were made using the irradiator and Elekta Precise linac facilities at the National Research Council of Canada. The objective was to characterize the chambers over the range of energies applicable to TG‐51 and determine whether each chamber met the requirements of a reference‐class instrument. Chamber settling, leakage current, ion recombination and polarity, and waterproofing sleeve effects were investigated, and absorbed dose calibration coefficients were obtained for and 6, 10, and 25 MV photon beams. Only thimble‐type chambers were considered in this investigation and were classified into three groups: (i) Reference chambers (“standard” Farmer‐type chambers and their derivatives traditionally used for beam output calibration); (ii) scanning chambers (typically volume chambers used for beam commissioning with 3‐D scanning phantoms); and (iii) microchambers (very small volume ion chambers used for small field dosimetry).

Results:

As might be expected, thimble chambers showed the most predictable performance and experimental factors were obtained with a relative uncertainty of 0.1%. The performance of scanning and microchambers was somewhat variable. Some chambers showed very good behavior but others showed anomalous polarity and recombination corrections that are not fully explained at present. For the well‐behaved chambers, agreement between measured and calculated factors was within 0.4%; for some chambers, differences of more than 1% were seen that may be related to the recombination/polarity results. Use of such chambers could result in significant errors in the determination of reference dose in the clinic.

Conclusions:

Based on the experimental evidence obtained here, specification for a reference‐class ionization chamber could be developed that would minimize the error in using a dosimetry protocol with calculated beam quality conversion factors. The experimental data obtained here for a wide range of thimble chambers can be used when choosing suitable detectors for reference dosimetry and are intended to be used in the upcoming update/addendum to the AAPM TG‐51 dosimetry protocol.
Experimental and theoretical dosimetry of a new polymer encapsulated iodine‐125 source—SmartSeed: Dosimetric impact of fluorescence x rays
Authors: Abboud F. , Hollows M. , Scalliet P. , Vynckier S.
Published: April 2010

Purpose: The detailed study of a new permanent iodine‐125 brachytherapy source, SmartSeed, is presented in this article. It is the first iodine seed made with biocompatible polymer and is manufactured by the IBt‐Bebig group.

Methods: Three dosimetric studies have been performed: The first one used thermoluminescent detectors in a solid water phantom with NIST (National Institute of Standards and Technology, USA) calibrated seeds, and two separate studies were of Monte Carlo photon transport calculations (MCNP5 code). The TG‐43U1 protocol was applied to derive dosimetric parameters for clinical applications.

Results: The radial dose function was determined at different distances ranging from 0.5 to 10 cm; and the anisotropy function at angles ranging from 0° to 350° in 10° increments. Monte Carlo calculations were performed in liquid water to obtain values for , , , and as recommended by the TG‐43U1 protocol for use in treatment planning system software. SmartSeed's biocompatible polymer capsule permits fluorescence x rays (3, 5, and 12 keV), generated by lead glass marker, to be present in the emission spectrum, influencing the dose rate constant. The impact on near field dosimetry in water from these x rays was also investigated and reported. The capsule also attenuates iodine‐125 energies much less than typical titanium encased sources, resulting in a highly isotropic source.

Conclusions: SmartSeed has a dose rate constant of , a radial dose function nearly identical to the IBt‐Bebig model I25.S06 seed, and a highly isotropic dose distribution. Fluorescence x rays account for the relatively low value of , yet their variable contribution to dosimetry arising from seed dimensional uncertainties is estimated to be .
Homogenized blocked arcs for multicriteria optimization of radiotherapy: Analytical and numerical solutions
Authors: Fenwick John D. , Pardo‐Montero Juan
Published: April 2010

Purpose:

Homogenized blocked arcs are intuitively appealing as basis functions for multicriteria optimization of rotational radiotherapy. Such arcs avoid an organ‐at‐risk (OAR), spread dose out well over the rest‐of‐body (ROB), and deliver homogeneous doses to a planning target volume (PTV) using intensity modulated fluence profiles, obtainable either from closed‐form solutions or iterative numerical calculations. Here, the analytic and iterative arcs are compared.

Methods:

Dose‐distributions have been calculated for nondivergent beams, both including and excluding scatter, beam penumbra, and attenuation effects, which are left out of the derivation of the analytic arcs. The most straightforward analytic arc is created by truncating the well‐known Brahme, Roos, and Lax (BRL) solution, cutting its uniform dose region down from an annulus to a smaller nonconcave region lying beyond the OAR. However, the truncation leaves behind high dose hot‐spots immediately on either side of the OAR, generated by very high BRL fluence levels just beyond the OAR. These hot‐spots can be eliminated using alternative analytical solutions “C” and “L,” which, respectively, deliver constant and linearly rising fluences in the gap region between the OAR and PTV (before truncation).

Results:

Measured in terms of PTV dose homogeneity, ROB dose‐spread, and OAR avoidance, C solutions generate better arc dose‐distributions than L when scatter, penumbra, and attenuation are left out of the dose modeling. Including these factors, L becomes the best analytical solution. However, the iterative approach generates better dose‐distributions than any of the analytical solutions because it can account and compensate for penumbra and scatter effects. Using the analytical solutions as starting points for the iterative methodology, dose‐distributions almost as good as those obtained using the conventional iterative approach can be calculated very rapidly.

Conclusions:

The iterative methodology is appropriate and useful for computing homogenized blocked arcs, as it produces better dose‐distributions than the analytic approaches and their obvious extensions, and can more straightforwardly be used to generate homogenized arcs for concave OARs. However, the analytical solutions provide promising starting points for the iterative algorithm, leading to fast convergence.
Simulation of image detectors in radiology for determination of scatter‐to‐primary ratios using Monte Carlo radiation transport codeMCNP/MCNPX
Authors: Smans Kristien , Zoetelief Johannes , Verbrugge Beatrijs , Haeck Wim , Struelens Lara , Vanhavere Filip , Bosmans Hilde
Published: April 2010

Purpose:The purpose of this study was to compare and validate three methods to simulate radiographic image detectors with the Monte Carlo softwareMCNP/MCNPXin a time efficient way.

Methods:The first detector model was the standard semideterministic radiography tally, which has been used in previous image simulation studies. Next to the radiography tally two alternative stochastic detector models were developed: A perfect energy integrating detector and a detector based on the energy absorbed in the detector material. Validation of three image detector models was performed by comparing calculated scatter‐to‐primary ratios (SPRs) with the published and experimentally acquired SPR values.

Results:For mammographic applications, SPRs computed with the radiography tally were up to 44% larger than the published results, while the SPRs computed with the perfect energy integrating detectors and the blur‐free absorbed energy detector model were, on the average, 0.3% (ranging from −3% to 3%) and 0.4% (ranging from −5% to 5%) lower, respectively. For general radiography applications, the radiography tally overestimated the measured SPR by as much as 46%. The SPRs calculated with the perfect energy integrating detectors were, on the average, 4.7% (ranging from −5.3% to −4%) lower than the measured SPRs, whereas for the blur‐free absorbed energy detector model, the calculated SPRs were, on the average, 1.3% (ranging from −0.1% to 2.4%) larger than the measured SPRs.

Conclusions:For mammographic applications, both the perfect energy integrating detector model and the blur‐free energy absorbing detector model can be used to simulate image detectors, whereas for conventional x‐ray imaging using higher energies, the blur‐free energy absorbing detector model is the most appropriate image detector model. The radiography tally overestimates the scattered part and should therefore not be used to simulate radiographic image detectors.
The noise power spectrum in CT with direct fan beam reconstruction
Authors: Baek Jongduk , Pelc Norbert J.
Published: April 2010

The noise power spectrum (NPS) is a useful metric for understanding the noise content in images. To examine some unique properties of the NPS of fan beam CT, the authors derived an analytical expression for the NPS of fan beam CT and validated it with computer simulations. The nonstationary noise behavior of fan beam CT was examined by analyzing local regions and the entire field‐of‐view (FOV). This was performed for cases with uniform as well as nonuniform noise across the detector cells and across views. The simulated NPS from the entire FOV and local regions showed good agreement with the analytically derived NPS. The analysis shows that whereas the NPS of a large FOV in parallel beam CT (using a ramp filter) is proportional to frequency, the NPS with direct fan beam FBP reconstruction shows a high frequency roll off. Even in small regions, the fan beam NPS can show a sharp transition (discontinuity) at high frequencies. These effects are due to the variable magnification and therefore are more pronounced as the fan angle increases. For cases with nonuniform noise, the NPS can show the directional dependence and additional effects.
Off‐label use of medical products in radiation therapy: Summary of the Report of AAPM Task Group No. 121a)
Authors: Thomadsen Bruce R. , Heaton H. Thompson , Jani Shirish K. , Masten Jeffery P. , Napolitano Mary E. , Ouhib Zoubir , Reft Chester S. , Rivard Mark J. , Robin T. Tydings , Subramanian Manny , Suleiman Orhan H.
Published: April 2010

Medical products (devices, drugs, or biologics) contain information in their labeling regarding the manner in which the manufacturer has determined that the products can be used in a safe and effective manner. The Food and Drug Administration (FDA) approves medical products for use for these specific indications which are part of the medical product's labeling. When medical products are used in a manner not specified in the labeling, it is commonly referred to as off‐label use. The practice of medicine allows for this off‐label use to treat individual patients, but the ethical and legal implications for such unapproved use can be confusing. Although the responsibility and, ultimately, the liability for off‐label use often rests with the prescribing physician, medical physicists and others are also responsible for the safe and proper use of the medical products. When these products are used for purposes other than which they were approved, it is important for medical physicists to understand their responsibilities. In the United States, medical products can only be marketed if officially cleared, approved, or licensed by the FDA; they can be used if they are not subject to or specifically exempt from FDA regulations, or if they are being used in research with the appropriate regulatory safeguards. Medical devices are either cleared or approved by FDA's Center for Devices and Radiological Health. Drugs are approved by FDA's Center for Drug Evaluation and Research, and biological products such as vaccines or blood are licensed under a biologics license agreement by FDA's Center for Biologics Evaluation and Research. For the purpose of this report, the process by which the FDA eventually clears, approves, or licenses such products for marketing in the United States will be referred to as approval. This report summarizes the various ways medical products, primarily medical devices, can legally be brought to market in the United States, and includes a discussion of the approval process, along with manufacturers’ responsibilities, labeling, marketing and promotion, and off‐label use. This is an educational and descriptive report and does not contain prescriptive recommendations. This report addresses the role of the medical physicist in clinical situations involving off‐label use. Case studies in radiation therapy are presented. Any mention of commercial products is for identification only; it does not imply recom‐mendations or endorsements of any of the authors or the AAPM. The full report, containing extensive background on off‐label use with several appendices, is available on the AAPM website (http://www.aapm.org/pubs/reports/).
The influence of initial outlines on manual segmentation
Authors: Sensakovic William F. , Starkey Adam , Roberts Rachael , Straus Christopher , Caligiuri Philip , Kocherginsky Masha , Armato Samuel G.
Published: April 2010

Purpose:

Initial outlines are often presented as an aid to reduce the time‐cost associated with manual segmentation and measurement of structures in medical images. This study evaluated the influence of initial outlines on manual segmentation intraobserver and interobserver precision.

Methods:

Three observers independently outlined all pleural mesothelioma tumors present in five computed tomography (CT) sections in each of 30 patient scans. After a lapse of time, each observer was presented with the same series of CT sections with the outlines of each observer superimposed as initial outlines. Each observer created altered outlines by altering the initial outlines to reflect their perception of the tumor boundary. Altered outlines were compared to original outlines using the Jaccard similarity coefficient. Intraobserver and interobserver precision of observer outlines were calculated by applying linear mixed effects analysis of variance models to the values. The percent of minor alterations (alterations that resulted in only slight changes in the initial outline) was also recorded.

Results:

The average value between pairs of observer original outlines was 0.371. The average value between pairs of observer outlines when altered from an identical initial outline was 0.796, indicating increased interobserver precision. The average difference between values of an observer's segmentation created by altering their own initial outline and when altering a different observer's initial outline was 0.476, indicating initial outlines strongly influence intraobserver precision. Observers made minor alterations on 74.5% of initial outlines with which they were presented.

Conclusions:

Intraobserver and interobserver precision were strongly dependent on the initial outline. These effects are likely due to the tendency of observers to make only minor corrections to initial outlines. This finding could impact observer study design, tumor growth assessment, computer‐aided diagnosis system validation, and radiation therapy target volume definition when initial outlines are used as an observer aid.
Technical Note: Fiducial markers for correlation of whole‐specimen histopathology with MR imaging at 7 tesla
Authors: McGrath Deirdre M. , Vlad Roxana M. , Foltz Warren D. , Brock Kristy K.
Published: April 2010

Purpose:

There is increasing interest in the registration of 3‐D histopathology with 3‐Din vivo imaging, for example, to validate tumor boundary delineation for targeted radiation cancer therapy. However, accurate correlation is compromised by tissue distortion induced by histopathological processing. Reference landmarks that are visible in both data sets are required. In this study, two iridescent acrylic paints, “Bronze” (containing iron oxide coated mica particles) and “Stainless Steel” (containing iron, chromium, and nickel), were evaluated for creating MRI‐visible and histology‐visible fiducial markers at 7 T, where resolution is more similar to histology, but artifacts are accentuated. Furthermore, a straight‐line paint‐track fiducial method was developed to assist in registration and 3‐D histopathology reconstruction.

Methods:

First, the paints were injected intoex vivo porcine tissue samples, which were MR imaged prefixation and postfixation, and subsequently prepared for hematoxylin and eosin staining to verify stability through histopathological processing. Second, the severity of marker susceptibility artifacts produced was compared while using spin‐echo and gradient‐echo MRI pulse sequences. Finally, multiple paint tracks were injected prefixation through an ex vivo canine prostate sample to validate the potential for line‐based registration between MR images of prefixation and postfixation tissue and whole mount histology slides.

Results:

The Stainless Steel paint produced excessive susceptibility artifacts and image distortion, while the Bronze paint created stable and appropriate markers in MRI and histology. The Bronze paint produced artifacts approximately three times larger in gradient‐echo than in spin‐echo MR images. Finally, the paint‐track fiducials were visible in the prefixation and postfixation MRI and on whole mount histology.

Conclusions:

The Bronze iridescent acrylic paint is appropriate for fiducial marker creation in MRI at 7 T. The straight‐line paint‐track fiducials may assist 3‐D histopathology reconstruction and can provide important information on the deformation effects of fixation, and hence may improve registration accuracy.
Computer‐aided measurement of liver volumes in CT by means of geodesic active contour segmentation coupled with level‐set algorithms
Authors: Suzuki Kenji , Kohlbrenner Ryan , Epstein Mark L. , Obajuluwa Ademola M. , Xu Jianwu , Hori Masatoshi
Published: April 2010

Purpose:

Computerized liver extraction from hepatic CT images is challenging because the liver often abuts other organs of a similar density. The purpose of this study was to develop a computer‐aided measurement of liver volumes in hepatic CT.

Methods:

The authors developed a computerized liver extraction scheme based on geodesic active contour segmentation coupled with level‐set contour evolution. First, an anisotropic diffusion filter was applied to portal‐venous‐phase CT images for noise reduction while preserving the liver structure, followed by a scale‐specific gradient magnitude filter to enhance the liver boundaries. Then, a nonlinear grayscale converter enhanced the contrast of the liver parenchyma. By using the liver‐parenchyma‐enhanced image as a speed function, a fast‐marching level‐set algorithm generated an initial contour that roughly estimated the liver shape. A geodesic active contour segmentation algorithm coupled with level‐set contour evolution refined the initial contour to define the liver boundaries more precisely. The liver volume was then calculated using these refined boundaries. Hepatic CT scans of 15 prospective liver donors were obtained under a liver transplant protocol with a multidetector CT system. The liver volumes extracted by the computerized scheme were compared to those traced manually by a radiologist, used as “gold standard.”

Results:

The mean liver volume obtained with our scheme was 1504 cc, whereas the mean gold standard manual volume was 1457 cc, resulting in a mean absolute difference of 105 cc (7.2%). The computer‐estimated liver volumetrics agreed excellently with the gold‐standard manual volumetrics (intraclass correlation coefficient was 0.95) with no statistically significant difference . The average accuracy, sensitivity, specificity, and percent volume error were 98.4%, 91.1%, 99.1%, and 7.2%, respectively. Computerized CT liver volumetry would require substantially less completion time (compared to an average of 39 min per case by manual segmentation).

Conclusions:

The computerized liver extraction scheme provides an efficient and accurate way of measuring liver volumes in CT.
Dose mapping of the rectal wall during brachytherapy with an array of scintillation dosimeters
Authors: Cartwright L. E. , Suchowerska N. , Yin Y. , Lambert J. , Haque M. , McKenzie D. R.
Published: April 2010

Purpose: In pelvic brachytherapy treatments, the rectum is an organ at risk. The authors have developed an array of scintillation dosimeters suitable for in vivo use that enables quality assurance of the treatment delivery and provides an alert to potential radiation accidents. Ultimately, this will provide evidence to direct treatment planning and dose escalation and correlate dose with the rectal response.

Methods: An array of 16 scintillation dosimeters in an insertable applicator has been developed. The dosimeters were calibrated simultaneously in a custom designed circular jig before use. Each dosimeter is optically interfaced to a set of pixels on a CCD camera located outside the treatment bunker. A customized software converts pixel values into dose rate and accumulates dose for presentation during treatment delivery. The performance of the array is tested by simulating brachytherapy treatments in a water phantom. The treatment plans were designed to deliver a known dose distribution on the surface of the rectal applicator, assumed to represent the dose to the rectal wall.

Results: The measured doses were compared to those predicted by the treatment plan and found to be in agreement to within the uncertainty in measurement, usually within 3%. The array was also used to track the progression of the source as it moved along the catheter. The measured position was found to agree with the position reported by the afterloader to within the measurement uncertainty, usually within 2 mm.

Conclusions: This array is capable of measuring the actual dose received by each region of the rectal wall during brachytherapy treatments. It will provide real time monitoring of treatment delivery and raise an alert to a potential radiation accident. Real time dose mapping in the clinical environment will give the clinician additional confidence to carry out dose escalation to the tumor volume while avoiding rectal side effects.