Biomedical subjects

Nzhde Agazaryan

Publications and source records attributed to Nzhde Agazaryan.

12 recordsLinked to original sources

PubMed2006

The biological effectiveness of antiproton irradiation.

BACKGROUND AND PURPOSE: Antiprotons travel through tissue in a manner similar to that for protons until they reach the end of their range where they annihilate and deposit additional energy. This makes them potentially interesting for radiotherapy. The aim of this study was to conduct the first ever measurements of the biological effectiveness of antiprotons. MATERIALS AND METHODS: V79 cells were suspended in a semi-solid matrix and irradiated with 46.7MeV antiprotons, 48MeV protons, or (60)Co gamma-rays. Clonogenic survival was determined as a function of depth along the particle beams. Dose and particle fluence response relationships were constructed from data in the plateau and Bragg peak regions of the beams and used to assess the biological effectiveness. RESULTS: Due to uncertainties in antiproton dosimetry we defined a new term, called the biologically effective dose ratio (BEDR), which compares the response in a minimally spread out Bragg peak (SOBP) to that in the plateau as a function of particle fluence. This value was approximately 3.75 times larger for antiprotons than for protons. This increase arises due to the increased dose deposited in the Bragg peak by annihilation and because this dose has a higher relative biological effectiveness (RBE). CONCLUSION: We have produced the first measurements of the biological consequences of antiproton irradiation. These data substantiate theoretical predictions of the biological effects of antiproton annihilation within the Bragg peak, and suggest antiprotons warrant further investigation.

Animals↗

PubMed2006

Brainstem and trigeminal nerve changes after radiosurgery for trigeminal pain.

PURPOSE: To evaluate the significance of radiological changes on follow-up MRIs after SRS for TN. MATERIALS AND METHODS: Thirty-seven patients with follow-up MRI because of paresthesias, bilateral treatment, or failure were analyzed regarding pain outcome and complications. Mean age was 64.4 years; 14 underwent previous treatment. Twenty-nine had ETN, 5 secondary TN due to tumor or multiple sclerosis, and 3 had atypical TN. Ninety gray was prescribed for 20 patients, 70 Gy for 5, and 80/85 Gy for 2. A 5-mm collimator was used in 32 (88.9%) cases. Mean follow-up was 15 months (range, 4-52 months). RESULTS: Excellent/good pain relief was sustained in 67% of cases at 13 months' follow-up. Enhancement on MRIs was observed in 21 cases (56.75%) with nerve enhancement in 9, pons enhancement in 4, pons-nerve enhancement in 4, and tumor enhancement in 4. Magnetic resonance images were unremarkable in 16 cases. Pain recurred in 4 cases (5.5-10 months). Pons enhancement correlated with pain relief (P = .0087) but not with nerve enhancement (P = .22). Incidence of slight paresthesias was 66.6%. No anesthesia dolorosa or ophthalmologic problems were observed. Paresthesias correlated with enhancement (P = .02), but not with brainstem volume encompassed by the 20%, 30%, and 50% isodoseline (P = .689, .525, .908). Enhancement free probability at 12 months was 48.5% (Kaplan-Meier). CONCLUSIONS: Pons enhancement seems to be prognostic for pain relief without higher incidence of complications. Pons volume irradiated did not predict enhancement occurrence. Radiation delivery to the brainstem-REZ interface seems to improve pain outcome, although more paresthesias should be expected.

Adult↗

PubMed2004

Degeneracy, frequency response and filtering in IMRT optimization.

This paper attempts to provide an answer to some questions that remain either poorly understood, or not well documented in the literature, on basic issues related to intensity modulated radiation therapy (IMRT). The questions examined are: the relationship between degeneracy and frequency response of optimizations, effects of initial beamlet fluence assignment and stopping point, what does filtering of an optimized beamlet map actually do and how could image analysis help to obtain better optimizations? Two target functions are studied, a quadratic cost function and the log likelihood function of the dynamically penalized likelihood (DPL) algorithm. The algorithms used are the conjugate gradient, the stochastic adaptive simulated annealing and the DPL. One simple phantom is used to show the development of the analysis tools used and two clinical cases of medium and large dose matrix size (a meningioma and a prostate) are studied in detail. The conclusions reached are that the high number of iterations that is needed to avoid degeneracy is not warranted in clinical practice, as the quality of the optimizations, as judged by the DVHs and dose distributions obtained, does not improve significantly after a certain point. It is also shown that the optimum initial beamlet fluence assignment for analytical iterative algorithms is a uniform distribution, but such an assignment does not help a stochastic method of optimization. Stopping points for the studied algorithms are discussed and the deterioration of DVH characteristics with filtering is shown to be partially recoverable by the use of space-variant filtering techniques.

Algorithms↗

PubMed2004

A methodology for verification of radiotherapy dose calculation.

OBJECT: A methodology for dosimetric verification of radiation therapy plans was developed and implemented. Dosimetric accuracy of clinically active intensity-modulated radiotherapy (IMRT) and intensity-modulated radiosurgery (IMRS) programs was assessed using this methodology. METHODS: The methodology included several dosimetric tasks that were performed to assess the dosimetric accuracy of a treatment plan. Absolute dosimetry of the composite plan was performed using an ionization chamber. Film dosimetry was performed for each individual field and for the multifield composite plan. Calculated dose distributions and film measurements were compared using software developed for the specific tasks. Two-dimensional maps of gamma index, dose difference, and distance-to-agreement were calculated and displayed. To date, good agreement between measurements and calculations has been observed in 160 clinical IMRT and IMRS plans. The largest observed absolute dose disagreement was -4.79%. The mean absolute dose difference was 0.26%, with a standard deviation of 1.75%. The authors specify a 3% dose difference and 3-mm distance as the scaling acceptability criteria for the gamma index calculations of the film measurement analysis. The planning and delivery system in clinical use has proven consistently to satisfy these criteria. CONCLUSIONS: The dosimetric verification methods and the software tools developed were both quantitative and clinically practical. The measurements and the analysis demonstrated that the IMRT and IMRS planning and delivery system in use was sufficiently accurate for highly conformal treatments.

Film Dosimetry↗

PubMed2004

Stereotactic radiotherapy for the treatment of acoustic neuromas.

OBJECT: The authors sought to assess the safety and efficacy of stereotactic radiotherapy when using a linear accelerator equipped with a micromultileaf collimator for the treatment of patients with acoustic neuromas. METHODS: Fifty patients harboring acoustic neuromas were treated with stereotactic radiotherapy between September 1997 and June 2003. Two patients were lost to follow-up review. Patient age ranged from 20 to 76 years (median 59 years), and none had neurofibromatosis. Forty-two patients had useful hearing prior to stereotactic radiotherapy. The fifth and seventh cranial nerve functions were normal in 44 and 46 patients, respectively. Tumor volume ranged from 0.3 to 19.25 ml (median 2.51 ml). The largest tumor dimension varied from 0.6 to 4 cm (median 2.2 cm). Treatment planning in all patients included computerized tomography and magnetic resonance image fusion and beam shaping by using a micromultileaf collimator. The planning target volume included the contrast-enhancing tumor mass and a margin of normal tissue varying from 1 to 3 mm (median 2 mm). All tumors were treated with 6-MV photons and received 54 Gy prescribed at the 90% isodose line encompassing the planning target volume. A sustained increase greater than 2 mm in any tumor dimension was defined as local relapse. The follow-up duration varied from 6 to 74 months (median 36 months). The local tumor control rate in the 48 patients available for follow up was 100%. Central tumor hypodensity occurred in 32 patients (67%) at a median of 6 months following stereotactic radiotherapy. In 12 patients (25%), tumor size increased 1 to 2 mm at a median of 6 months following stereotactic radiotherapy. Increased tumor size in six of these patients was transient. In 13 patients (27%), tumor size decreased 1 to 14 mm at a median of 6 months after treatment. Useful hearing was preserved in 39 patients (93%). New facial numbness occurred in one patient (2.2%) with normal fifth cranial nerve function prior to stereotactic radiotherapy. New facial palsy occurred in one patient (2.1 %) with normal seventh cranial nerve function prior to treatment. No patient's pretreatment dysfunction of the fifth or seventh cranial nerve worsened after stereotactic radiotherapy. Tinnitus improved in six patients and worsened in two. CONCLUSIONS: Stereotactic radiotherapy using field shaping for the treatment of acoustic neuromas achieves high rates of tumor control and preservation of useful hearing. The technique produces low rates of damage to the fifth and seventh cranial nerves. Long-term follow-up studies are necessary to confirm these findings.

Actuarial Analysis↗

PubMed2004

A feasibility study of 18F-fluorodeoxyglucose positron emission tomography targeting and simultaneous integrated boost for intensity-modulated radiosurgery and radiotherapy.

OBJECT: The authors hypothesized that the efficacy of intensity-modulated radiation therapy (IMRT) can be enhanced by selectively increasing the radiation dose to the biologically active positron emission tomography (PET)-documented positive tumor subregions while simultaneously maintaining the overall clinically established target dose. METHODS: The authors undertook a feasibility study to evaluate IMRT PET/computerized tomography (CT) protocol for boost treatment in selected cancer patients. Prior to treatment, FDG-PET and CT scans were acquired using an integrated PET/CT scanner, ensuring accurate correlation between image sets. After acquisition, tumor volume and objects-at-risk (OARs) were outlined on the CT scans; any PET-positive tumor subregions were similarly outlined. Daily dosages of 1.8 to 2 Gy were prescribed to tumor volume and the margin whereas additional dosages of 10 to 20% were delivered to PET-positive subregions. Dosage-volume histogram-derived constraints were used in inverse planning to specify the desired dose to one or more PET-positive tumor subregions, CT-delineated tumor volume, and OARs. The IMRT treatment was delivered using a micromultileaf collimator. Simultaneous integrated boost radiation was successfully delivered using IMRT with PET/CT planning. Excellent dose conformality was achieved in the tumor volume and the dose to PET-positive tumor subregions was increased while minimizing the dose to OARs. CONCLUSIONS: When coupled with IMRT, PET/CT scanning allows dose escalation to biologically active subregions within the tumor volume. Further study is needed to determine if dose escalation to FDG-PET-active sites correlates with improved treatment outcome. Finally, in extracranial sites, PET scanning should only be performed with a dedicated PET/CT device because present image fusion technologies are inadequate for accurately registering deformable objects.

Brain Neoplasms↗

PubMed2004

Spinal lesions treated with Novalis shaped beam intensity-modulated radiosurgery and stereotactic radiotherapy.

OBJECT: Spinal radiosurgery was implemented to improve quality of life (QOL) in patients with malignancies. It may also be applicable to the treatment of benign lesions. METHODS: Between July 2002 and January 2004, 14 patients harboring 22 lesions were treated; 13 received single-dose stereotactic radiosurgery. Six were women. The mean age was 60.2 years (range 48-82 years). There were 11 metastases, two neurofibromas, and one meningioma. Six lesions were cervical, 10 thoracic, and six lumbar. Ten patients suffered pain, three paresthesias, two weakness, and three were asymptomatic. Seven patients underwent spinal surgery, with four receiving instrumentation. Twelve patients underwent conventional irradiation before stereotactic radiosurgery/stereotactic radiotherapy. A mean dose of 12+/-2.7 Gy (range 8-21 Gy) was prescribed to the 91% isodose line (range 85-97%). The mean tumor volume was 25+/-27.1 ml (range 0.75-91.8 ml). Treatment was planned using intensity-modulated radiosurgery (IMRS) fields in 15 cases, dynamic arcs in five, and conformal beams in two. The mean follow-up period was 6.1+/-3.9 months (range 1-16 months). Three patients became pain free and four experienced considerable relief. Weakness improved in the two patients with this preoperative symptom and the asymptomatic patients remained so. Four lesions decreased in size, five remained stable, seven progressed, and six were not followed up (two patients died before follow up). Four patients in all died, three of systemic disease and one of thoracic lesion progression. No complications due to shaped beam and IMRS/intensity-modulated radiotherapy (IMRT) techniques were observed. CONCLUSIONS: Shaped beam and IMRS/IMRT involving the Novalis system may delay neurological deterioration, improving QOL. The lack of complication suggests that higher doses can be delivered to improve the control rate in patients with metastases.

Aged↗

PubMed2003

The effects of tumor motion on planning and delivery of respiratory-gated IMRT.

The purpose of this study is to investigate the effects of object motion on the planning and delivery of IMRT. Two phantoms containing objects were imaged using CT under a variety of motion conditions. The effects of object motion on axial CT acquisition with and without gating were assessed qualitatively and quantitatively. Measurements of effective slice width and position for the CT scans were made. Mutual information image fusion was adapted for use as a quantitative measure of object deformation in CT images. IMRT plans were generated on the CT scans of the moving and gated object images. These plans were delivered with motion, with and without gating, and the delivery error between the moving deliveries and a nonmoving delivery was assessed using a scalable vector-based index. Motion during CT acquisition produces motion artifact, object deformation, and object mispositioning, which can be substantially reduced with gating. Objects that vary in cross section in the direction of motion exhibit the most deformation in CT images. Mutual information provides a useful quantitative estimate of object deformation. The delivery of IMRT in the presence of target motion significantly alters the delivered dose distribution in relation to the planned distribution. The utilization of gating for IMRT treatment, including imaging, planning, and delivery, significantly reduces the errors introduced by object motion.

Artifacts↗

PubMed2003

Segmental and dynamic intensity-modulated radiotherapy delivery techniques for micro-multileaf collimator.

A leaf sequencing algorithm has been implemented to deliver segmental and dynamic multileaf collimated intensity-modulated radiotherapy (SMLC-IMRT and DMLC-IMRT, respectively) using a linear accelerator equipped with a micro-multileaf collimator (mMLC). The implementation extends a previously published algorithm for the SMLC-IMRT to include the dynamic MLC-IMRT method and several dosimetric considerations. The algorithm has been extended to account for the transmitted radiation and minimize the leakage between opposing and neighboring leaves. The underdosage problem associated with the tongue-and-groove design of the MLC is significantly reduced by synchronizing the MLC leaf movements. The workings of the leaf sequencing parameters have been investigated and the results of the planar dosimetric investigations show that the sequencing parameters affect the measured dose distributions as intended. Investigations of clinical cases suggest that SMLC and DMLC delivery methods produce comparable results with leaf sequences obtained by root-mean-square (RMS) errors specification of 1.5% and lower, approximately corresponding to 20 or more segments. For SMLC-IMRT, there is little to be gained by using an RMS error specification smaller than 2%, approximately corresponding to 15 segments; however, more segments directly translate to longer treatment time and more strain on the MLC. The implemented leaf synchronization method does not increase the required monitor units while it reduces the measured TG underdoses from a maximum of 12% to a maximum of 3% observed with single field measurements of representative clinical cases studied.

Algorithms↗

PubMed2003

Patient specific quality assurance for the delivery of intensity modulated radiotherapy.

A patient specific quality assurance program has been developed to facilitate the clinical implementation of intensity modulated radiotherapy (IMRT) delivered using a micro-multileaf collimator. The methodology includes several dosimetric tasks that are performed prior to the treatment of each patient. Film dosimetry is performed for each individual field and for the multifield composite plan. Individual field measurements are performed at a depth of 5 cm in a water equivalent slab phantom; export of dose calculations from the treatment planning system is similarly specified. For the composite distribution, parameters from the patient plan are applied to an IMRT phantom, and film is exposed in an axial orientation. Distributions are compared with the aid of software developed for the specific tasks. The measured and calculated dose distributions can be superimposed and positioned graphically using move, rotate, and mirror tools, as well as by specifying isocenter coordinates and using fiducial marks. Horizontal and vertical profiles are available for analysis. Dose difference, distance-to-agreement, and gamma index, the minimum scaled multidimensional distance between a measurement and a calculation point determined in combined dose and physical distance space, are calculated along a specified isodose line and displayed. gamma provides an excellent measure of disagreement between measurement and calculation for complex intensity distributions. We specify 3% dose difference and 3 mm distance as our scaling acceptability criteria. Absolute dosimetry for each composite plan is performed using an ionization chamber. To date, excellent agreement between measurements and calculations has been observed.

Humans↗

PubMed2003

A seed specific dose kernel method for low-energy brachytherapy dosimetry.

We describe a method for independently verifying the dose distributions from pre- and post-implant brachytherapy source distributions. Monte Carlo calculations have been performed to characterize the three-dimensional dose distribution in water phantom from a low-energy brachytherapy source. The calculations are performed in a voxelized, Cartesian coordinate geometry and normalized based upon a separate Monte Carlo calculation for the seed specific air-kerma strength to produce an absolute dose grid with units of cGy hr(-1) x U(-1). The seed-specific, three-dimensional dose grid is stored as a text file for processing using a separate visual basic program. This program requires the coordinate positions of each seed in the pre- or post-plan and sums the kernel file for a three-dimensional composite dose distribution. A kernel matrix size of 81x81x81 with a voxel size of 1.0x1.0x1.0 mm3 was chosen as a compromise between calculation time, kernel size, and truncation of the stored dose distribution as a function of radial distance from the midpoint of the seed. Good agreement is achieved for a representative pre- and post-plan comparison versus a commercial implementation of the TG-43 brachytherapy dosimetry protocol.

Algorithms↗

PubMed2002

An evaluation of gating window size, delivery method, and composite field dosimetry of respiratory-gated IMRT.

A respiratory gating system has been developed based on a commercial patient positioning system. The purpose of this study is to investigate the ability of the gating system to reproduce normal, nongated IMRT operation and to quantify the errors produced by delivering a nongated IMRT treatment onto a moving target. A moving phantom capable of simultaneous two-dimensional motion was built, and an analytical liver motion function was used to drive the phantom. Studies were performed to assess the effect of gating window size and choice of delivery method (segmented and dynamic multileaf collimation). Additionally, two multiple field IMRT cases were delivered to quantify the error in gated and nongated IMRT with motion. Dosimetric error between nonmoving and moving deliveries is related to gating window size. By reducing the window size, the error can be reduced. Delivery error can be reduced for both dynamic and segmented delivery with gating. For the implementation of dynamic IMRT delivery in this study, dynamic delivery was found to generate larger delivery errors than segmented delivery in most cases studied. For multiple field IMRT delivery, the largest errors were generated in regions where high field modulation was present parallel to the axis of motion. Gating was found to reduce these large errors to clinically acceptable levels.

Artifacts↗