Search PubMed⌕ Search

Biomedical subjects

Lei Dong

Publications and source records attributed to Lei Dong.

At least 55 records · Page 3Linked to original sources

Comparison of treatment volumes and techniques in prostate cancer radiation therapy.

OBJECTIVE: To compare dose-volume histograms (DVHs) for 3 target volumes (group 1, prostate + seminal vesicles + pelvic lymph nodes; group 2, prostate + seminal vesicles; group 3, prostate only) to determine the difference in dose to normal structures (rectum, bladder, and femoral heads) while controlling for target dose using 3-dimensional conformal radiation therapy (3DCRT) versus intensity modulated radiation therapy (IMRT). METHODS: Ten patients with localized prostate cancer were randomly selected. 3DCRT and IMRT planning were done to deliver 75.6 Gy to the prostate, 50.4 Gy to the pelvic nodes, and 55.8 Gy to the seminal vesicles at a standard fractionation of 1.8 Gy. An additional plan delivering 75.6 Gy to the seminal vesicles using IMRT was run. DVHs were compared for 3DCRT and IMRT. RESULTS: In all 3 groups, the percent rectum receiving > or =70 Gy, > or =60 Gy, and > or =40 Gy was significantly less for IMRT than for 3DCRT. Increasing target volumes, as necessary for pelvic nodal irradiation, overall did not result in higher rectal doses for IMRT. With 3DCRT, however, larger target volumes did increase the amount of rectum irradiated. Similar results were obtained for the femoral heads whereas results for the bladder were mixed. CONCLUSION: When compared with 3DCRT, IMRT delivered equivalent or higher doses to the target volume with greater sparing of critical organs. Because dose-volume parameters have been shown to relate to toxicity, IMRT would appear to be the favored technique for prostate cancer radiation, particularly with regard to nodal treatment.

Dose Fractionation, Radiation↗

The leucyl aminopeptidase from Helicobacter pylori is an allosteric enzyme.

This study describes the cloning, genetic analysis and biochemical characterization of a leucyl aminopeptidase (LAP) from Helicobacter pylori. A gene encoding LAP was cloned from H. pylori and the expressed 55 kDa protein displayed homology to aminopeptidases from Gram-negative bacteria, plants and mammals. This LAP demonstrated amidolytic activity against L-leucine-p-nitroanilide. Optimal activity was observed at pH 8.0 and 45 degrees C, with V(max) of 232 mumol min(-1) (mg protein)(-1) and S(0.5) of 0.65 mM. The data suggest that LAP could be allosteric (n(H)=2.27), with regulatory homohexamers, and its activity was inhibited by ion chelators and enhanced by divalent manganese, cobalt and nickel cations. Bestatin inhibited both LAP activity (IC(50)=49.9 nM) and H. pylori growth in vitro. The results point to the potential use of LAP as a drug target to develop novel anti-H. pylori agents.

Allosteric Regulation↗

Dosimetric accuracy of Kodak EDR2 film for IMRT verifications.

Patient-specific intensity-modulated radiotherapy (IMRT) verifications require an accurate two-dimensional dosimeter that is not labor-intensive. We assessed the precision and reproducibility of film calibrations over time, measured the elemental composition of the film, measured the intermittency effect, and measured the dosimetric accuracy and reproducibility of calibrated Kodak EDR2 film for single-beam verifications in a solid water phantom and for full-plan verifications in a Rexolite phantom. Repeated measurements of the film sensitometric curve in a single experiment yielded overall uncertainties in dose of 2.1% local and 0.8% relative to 300 cGy. 547 film calibrations over an 18-month period, exposed to a range of doses from 0 to a maximum of 240 MU or 360 MU and using 6 MV or 18 MV energies, had optical density (OD) standard deviations that were 7%-15% of their average values. This indicates that daily film calibrations are essential when EDR2 film is used to obtain absolute dose results. An elemental analysis of EDR2 film revealed that it contains 60% as much silver and 20% as much bromine as Kodak XV2 film. EDR2 film also has an unusual 1.69:1 silver:halide molar ratio, compared with the XV2 film's 1.02:1 ratio, which may affect its chemical reactions. To test EDR2's intermittency effect, the OD generated by a single 300 MU exposure was compared to the ODs generated by exposing the film 1 MU, 2 MU, and 4 MU at a time to a total of 300 MU. An ion chamber recorded the relative dose of all intermittency measurements to account for machine output variations. Using small MU bursts to expose the film resulted in delivery times of 4 to 14 minutes and lowered the film's OD by approximately 2% for both 6 and 18 MV beams. This effect may result in EDR2 film underestimating absolute doses for patient verifications that require long delivery times. After using a calibration to convert EDR2 film's OD to dose values, film measurements agreed within 2% relative difference and 2 mm criteria to ion chamber measurements for both sliding window and step-and-shoot fluence map verifications. Calibrated film results agreed with ion chamber measurements to within 5 % /2 mm criteria for transverse-plane full-plan verifications, but were consistently low. When properly calibrated, EDR2 film can be an adequate two-dimensional dosimeter for IMRT verifications, although it may underestimate doses in regions with long exposure times.

Dose-Response Relationship, Radiation↗

Retrospective analysis of 2D patient-specific IMRT verifications.

We performed 858 two-dimensional (2D) patient-specific intensity modulated radiotherapy verifications over a period of 18 months. Multifield, composite treatment plans were measured in phantom using calibrated Kodak EDR2 film and compared with the calculated dose extracted from two treatment planning systems. This research summarizes our findings using the normalized agreement test (NAT) index and the percent of pixels failing the gamma index as metrics to represent the agreement between measured and computed dose distributions. An in-house dose comparison software package was used to register and compare all verifications. We found it was important to use an automatic positioning algorithm to achieve maximum registration accuracy, and that our automatic algorithm agreed well with anticipated results from known phantom geometries. We also measured absolute dose for each case using an ion chamber. Because the computed distributions agreed with ion chamber measurements better than the EDR2 film doses, we normalized EDR2 data to the computed distributions. The distributions of both the NAT indices and the percentage of pixels failing the gamma index were found to be exponential distributions. We continue to use both the NAT index and percent of pixels failing gamma with 5%/3 mm criteria to evaluate future verifications, as these two metrics were found to be complementary. Our data showed that using 2%/2 mm or 3%/3 mm criteria produces results similar to those using 5%/3 mm criteria. Normalized comparisons that have a NAT index greater than 45 and/or more than 20% of the pixels failing gamma for 5%/3 mm criteria represent outliers from our clinical data set and require further analysis. Because our QA verification results were exponentially distributed, rather than a tight grouping of similar results, we continue to perform patient-specific QA in order to identify and correct outliers in our verifications. The data from this work could be useful as a reference for other clinics to indicate anticipated trends in 2D verifications under various conditions.

Algorithms↗

Dose sculpting with generalized equivalent uniform dose.

With intensity-modulated radiotherapy (IMRT), a variety of user-defined dose distribution can be produced using inverse planning. The generalized equivalent uniform dose (gEUD) has been used in IMRT optimization as an alternative objective function to the conventional dose-volume-based criteria. The purpose of this study was to investigate the effectiveness of gEUD optimization to fine tune the dose distributions of IMRT plans. We analyzed the effect of gEUD-based optimization parameters on plan quality. The objective was to determine whether dose distribution to selected structures could be improved using gEUD optimization without adversely altering the doses delivered to other structures, as in sculpting. We hypothesized that by carefully defining gEUD parameters (EUD0 and n) based on the current dose distributions, the optimization system could be instructed to search for alternative solutions in the neighborhood, and we could maintain the dose distributions for structures already satisfactory and improve dose for structures that need enhancement. We started with an already acceptable IMRT plan optimized with any objective function. The dose distribution was analyzed first. For structures that dose should not be changed, a higher value of n was used and EUD0 was set slightly higher/lower than the EUD value at the current dose distribution for critical structures/targets. For structures that needed improvement in dose, a higher to medium value of n was used, and EUD0 was set to the EUD value or slightly lower/higher for the critical structure/target at the current dose distribution. We evaluated this method in one clinical case each of head and neck, lung and prostate cancer. Dose volume histograms, isodose distributions, and relevant tolerance doses for critical structures were used for the assessment. We found that by adjusting gEUD optimization parameters, the dose distribution could be improved with only a few iterations. A larger value of n could lead to faster convergence and a medium value of n could result in a search in a broader area. Such improvement could also be achieved by optimization based on other criteria, but the gEUD-based method has the advantage of efficiency and flexibility. Therefore, gEUD-based optimization can be used as a tool to improve IMRT plans by adjusting the planning parameters, thereby making dose sculpting feasible.

Algorithms↗

Bactericidal and morphological effects of NE-2001, a novel synthetic agent directed against Helicobacter pylori.

The antibacterial activities of NE-2001 were tested against 24 clinical isolates of Helicobacter pylori and compared with those of amoxicillin, clarithromycin, metronidazole, and furazolidone. The MIC(50) and MIC(90) of this synthetic compound on the isolates were 8 and 16 mug/ml, respectively. This action was highly selective against Helicobacter pylori; there was a >4-fold difference between the concentration of NE-2001 required to inhibit the growth of Helicobacter pylori and that required to inhibit the growth of common aerobic and anaerobic bacteria. Exposure of Helicobacter pylori (ATCC43504) to NE-2001 at the MIC (4 mug/ml), or at a greater concentration, resulted in an extensive loss of viability. The phenomenon was also observed at pH levels between 3.0 and 7.0. When two clinical Helicobacter pylori strains were successively cultured at subinhibitory concentrations of NE-2001, no significant changes in the bactericidal effects were found. The morphological alterations of Helicobacter pylori cells (ATCC43504), exposed to NE-2001 at various concentrations for 6 h, were observed using transmission electron microcopy. The bacterium displayed features such as swelling, vacuole-like structures in the cytoplasm, and cell destruction following exposure to NE-2001. The efficacy of NE-2001 was maintained when evaluated in eight clinical isolates resistant to metronidazole and five isolates resistant to both metronidazole and clarithromycin (MIC ranging between 4 and 16 mug/ml). The above-described results suggest that NE-2001 may have the potential to be developed as a candidate agent for the treatment of Helicobacter pylori infection.

Adult↗

[Experimental study on harmonic detection of methane by use of a digital lock-in amplifier].

The harmonic detection of methane at 6105.3694 cm(-1) was measured by use of a digital lock-in amplifier (SR830) remotely controlled by a computer. The programme was written by Visual Basic 6.0 because it has strong function and a friendly appearance. The experimental results are in agreement with theoretical analysis, which fully confirms that a better signal-to-noise ratio (SNR) can be achieved in the high-harmonics detection of trace gases by the digital lock-in amplifier. The method can be applicable to the highly sensitive detection of pollution gases.

Air Pollutants↗

[A clinical study of non-erosive reflux disease].

OBJECTIVE: [corrected] To investigate the differences and similarities between non-erosive reflux disease (NERD) and reflux disease (RE). METHODS: This study covered 30 patients who were grouped by endoscopy into the cases of NERD (n=17) or RE (n=13). The two groups' symptom, mentality, and damage to life quality were compared. Biopsy was performed at 3 cm above LES in oesophagus. The patients were placed under ambulatory 24-h oesophageal pH and Bilitec2000 monitoring. And their responses to the same anti-reflux treatment were evaluated. RESULTS: (1) The proportion of female (58.82%) in NERD group was much higher than that (15.38%) in RE group (P<0.05). (2) There was no remarkable difference in symptom, damage to life quality between the NERD and RE groups (P>0.05). But in respect to mentality, the NERD group had significantly higher anxiety and depression scores than did the RE group (P<0.05). (3) No noticeable difference in the pathological results of biopsy was seen between the NERD and RE groups (P>0.05). (4) The NERD group had less abnormal reflux, compared with the RE group (P<0.05). (5) The NERD group gave less response to treatment, compared to the RE group (P<0.05). CONCLUSION: NERD may be a kind of reflux disease different from RE.

Adult↗

[Effects of intrahippocampal microinjection of motilin on interdigestive migrating myoelectrical complexes of rat duodenum].

OBJECTIVE: To explore the effects of intrahippocampal injection of motilin on interdigestive migrating myoelectrical complex (MMC) of rat duodenum. METHODS: Adult SD rats of either sex were subjected to injection of 0.5 microl motilin (0.74 nmol/microl) through the guiding cannula stereotaxically implanted into the hippocampus previously. Interdigestive MMC of the duodenum was recorded by RM6240B multilead physiological recording system. RESULTS: After motilin injection into the hippocampus, duodenal MMC cycle was significantly shortened, but the amplitude and frequency of phase III were increased without affecting the duration of phase III. The effect of motilin injection into the hippocampus on MMC was completely abolished by subdiaphragmal vagotomy but not affected by intravenously injected atropine, phentolamine or propranolol. Anti-motilin serum could partly abolish the effects of motilin on MMC. CONCLUSIONS: Motilin injection into the hippocampus have effects on the duration of duodenal MMC cycle and the amplitude and frequency of phase III, which may rely on the effect of noncholinergic and nonadrenergic neurons on duodenal smooth muscle or the increase of local motilin via hippocampus-hypothalamus-brain stem-vagus pathway. The hippocampus plays an important role in duodenal MMC.

Animals↗

[Distribution and role of motilin receptor in the amygdala of rats].

OBJECTIVE: To explore the distribution and role of motilin receptor in the amygdala of rats. METHODS: The distribution of motilin receptor in the amygdala was detected by immunohistochemistry in adult SD rats of either sex. The duodenal interdigestive migrating myoelectric complex (MMC) was recorded and analyzed for investigating the role of motilin receptor in the amygdala. RESULTS: Motilin receptors were detected in the amygdala of rats. The medial amygdaloid nucleus contained the greatest amount of motilin receptors, which was also abound in the basolateral nucleus of the amygdala but less abundant in the basomedial nucleus of the amygdala, central amygdaloid nucleus and lateral amygdaloid nucleus. The binding of motilin receptors and motilin in the amygdala caused shortening of duodenal MMC cycle duration and increased amplitude and frequency of phase III. The effects were completely abolished by subdiaphragmal vagotomy but not by intravenous injection of atropine, phentolamine or propranolol. Anti-motilin serum partially abolished these effects, and destruction of the basolateral nucleus of the amygdala had no effects on duodenal MMC. CONCLUSIONS: Motilin receptors are present in all the subnuclei of the amygdala. The effects of microinjection of motilin in the amygdala on duodenal MMC might rely on either the effects of noncholinergic and nonadrenergic neurons on the duodenal smooth muscle, or increase in local motilin via amygdala-hypothalamus-brain stem-vagus pathway, indicating the important role of motilin receptor in the amygdala in duodenal MMC regulation.

Amygdala↗

[Study on the relationship between aspirin resistance and incidence of myonecrosis after non-emergent percutaneous coronary intervention].

OBJECTIVE: To investigate the occurrence of aspirin resistance in coronary heart disease (CHD) patients and its influence on myonecrosis among patients undergoing non-emergent percutaneous coronary intervention (PCI). METHODS: 256 CHD patients who have been on aspirin (100 mg/d) for at least 7 days were recruited based on aspirin responsiveness determination. All the patients were divided into two groups: aspirin-resistant group and aspirin-sensitive group. For all patients scheduled for non-emergent PCI, a loading dose of 300 mg of clopidogrel was given at least 12 h before PCI and a 75 mg maintenance dose was given every morning before and after PCI. The incidence of myonecrosis was evaluated by the levels of creatine kinase-myocardial band (CK-MB) and troponin I (TnI) before and after PCI. RESULTS: Aspirin resistance was found in 67 (26.2%) patients and 189 (73.8%) patients were aspirin-sensitive. There was a significantly higher proportion of female subjects in the aspirin-resistant group. The incidence of any CK-MB elevation was 38 (56.7%) in aspirin-resistant group and 42 (22.2%) in aspirin-sensitive group (P < 0.01). The elevation of TnI was observed in 41 (61.2%) of the aspirin-resistant group and in 67 (35.4%) of the aspirin-sensitive group (P < 0.05). Multivariate analysis revealed that aspirin resistance was an independent predictor for CK-MB elevation after PCI (OR = 2.5; 95% CI 1.5 to 6.5; P < 0.05). CONCLUSION: Aspirin resistance exists in some CHD patients, which increases the risk of myonecrosis following non-emergent PCI.

Aged↗

[Changes of gastrointestinal myoelectric activity and bile acid pool during cholesterol gallstone formation in guinea pigs].

OBJECTIVE: To investigate the changes of gastrointestinal migrating myoelectric complex (MMC) and bile acid pool size during cholesterol gallstone formation in guinea pigs. METHODS: Seventy-five guinea pigs were randomized into 5 equal groups and given normal diet for 8 weeks, 1% cholesterol diet for 2, 4, and 8 weeks, and cholesterol diet with Vitamin C for 8 weeks, respectively. At the end of the feeding period, the gallbladder motility was assessed by deploying 4 bipolar silver electrodes on the antrum, duodenum, jejunum and ileum. Seven days later, MMC was recorded and the total bile acid pool size measured according to the isotope dilution method. RESULTS: After cholesterol feeding, the gallbladder motility declined in 4- and 8-week groups, which showed a reduction of bile acid pool size by 42.75% (P<0.05) and 57.24% (P<0.05), respectively. Compared to the control group, MMCs started mostly in the duodenum. MMC cycle duration was prolonged in the duodenum by 1.32 times in 4-week group (P<0.05) and 1.44 times in 8 week group (P<0.05) whereas MMC amplitude was lowered in the duodenum by 40.91% in 4-week group (P<0.05) and 60.17% in 8 week group (P<0.05). Supplementation of vitamin C caused changes in MMC similar to those observed in the guinea pigs of 2-week group. CONCLUSIONS: High-cholesterol diet inhibits MMC activity and reduces bile acid pool size in guinea pigs, which, along with impairment of the gallbladder motility, contributes to the formation of cholesterol stone, whereas vitamin C supplement in the diet may help prevent cholelithiasis.

Animals↗

Effect of SC-435 on the gastrointestinal migrating myoelectric complex in guinea pigs.

OBJECTIVE: To determine whether SC-435, a new ileal apical sodium-codependent bile acid transporter (IBAT) inhibitor, can alter the gastrointestinal motility in guinea pigs. METHODS: Sixty guinea pigs received regular diet or IBAT inhibitor (SC-435) diet for 2, 4, and 8 weeks, respectively. At the end of the feeding period, the gallbladder motility was assessed and then four bipolar silver electrodes were implanted on the antrum, duodenum, jejunum, and ileum. Seven days later, migrating motor complex (MMC) was recorded and the total bile acid pool size was measured according to the isotope dilution principle in the meantime. RESULTS: After feeding SC435, the gallbladder motility was declined in the 4-week group and the 8-week group. The bile acid pool size decreased by 17.11% (P <0.05) in the 4-week group and 48.35% (P < 0.05) in the 8-week group. The places of origin of MMC were changed where antral origins (37%) and duodenal origins (46%) decreased whereas jejunal origins (17%) increased. The MMC cycle period was prolonged in the duodenum (1.16 times in the 4-week group, P < 0.05; 1.38 times in the 8-week group, P < 0.05) whereas MMC amplitude fell in the duodenum (10.58% in the 4-week group, P <0.05; 49.17% in the 8-week group, P <0.05). There were not significant differences in all parameters of MMC between the control group and the 2-week group in guinea pigs. CONCLUSION: The IBAT inhibitor (SC-435) reduces the bile acid pool size and inhibits the MMC cycle activity. MMC is related to the enterohepatic circulation of bile acids, which is consistent with the changes of the bile acid pool size in guinea pigs.

Animals↗

[Correlation between blood flow velocity of feeding arteries and microvessel density of hepatocellular carcinoma].

OBJECTIVE: To evaluate the correlation between the mean of time blood flow velocity (TVmean) of feeding artery around hepatocellular carcinoma (HCC) and the microvessel density (MVD) in relation to tumor cell differentiation, and to evaluate the usefulness of TVmean as a noninvasive preoperative marker of biologic characteristic of HCC. METHODS: To measure TVmean of feeding arteries around the HCC in 45 patients before operation and TVmean of minute arteries in hepatic tissue in 45 normal subjects by ultrasonographic examination. Tumor cell differentiation grade was determined by routine histopathological staining. Tumor MVD was measured by immunohistochemical staining with monoclonal antibodies against F VIII RAg of excised HCC. Correlationship between TVmean of feeding arteries and MVD of HCC was studied. RESULTS: A linear correlation between TVmean of feeding arteries around the tumors of HCC and MVD of HCC tissue (r = 0.794, y = 18.2764 + 1.5544x) was obtained. With TVmean > or = 21.3 cm/s, the positive and negative predictive values of poorly differentiated HCC were 97.4% and 87.5%, respectively. With TVmean < 21.3 cm/s, those of well differentiated HCC were 88.5% and 97.3%, respectively. The degree of reliability of calculating HCC cell differentiation according to TVmean was 89.5%. CONCLUSION: Tumor growth and cellular differentiation, the two major factors affecting prognosis of HCC, may be evaluated by TVmean of feeding arteries around the tumor. It offers a useful preoperative information for predicting prognosis of HCC patients.

Adult↗

Characterization of a specific phage-displayed Peptide binding to vasculature of human gastric cancer.

Antivascular therapy provides a promising method for anticancer therapy. But targeting to gastric cancer vessels is nonselective due in part to the lack of specific cell-surface receptors identified on target vascular cells. Herein we used in vivo screening of phage displayed peptide library to identify some peptides that bind selectively to endothelial cells of human gastric cancer rather than nonendothelial cells. After four rounds of selection, one phage was obtained with a cyclic 7-mer peptide CGNSNPKSC homing to human gastric adenocarcinoma . There was a 4.6 approximately 137.26-fold increase in the number of the selected phage in gastric cancer xenograft in comparision with control organs brain, heart, liver, spleen and kidney. Immunohistochemistry in mouse and human tissue showed that this phage peptide only bind to the endothelial cells of human gastric cancer. This peptide was observed only specific binding to HUVEC not to SGC-7901, Eca-109, LoVo and Hep-G2 by ELISA. The competitive and inhibitory result between the synthetic CGNSNPKSC peptide and the phage displaying the peptide CGNSNPKSC on HUVEC and in vivo was also confirmed its specific binding effect. This peptide may be a possible candidate for targeted drug delivery in antivascular therapy.

Angiogenesis Inhibitors↗

Comparison of rectal dose-wall histogram versus dose-volume histogram for modeling the incidence of late rectal bleeding after radiotherapy.

PURPOSE: To compare the fits of normal-tissue complication probability (NTCP) models based on rectal dose-wall histograms (DWHs) vs. dose-volume histograms (DVHs) when the two are used to analyze a common set of late rectal toxicity data. METHODS AND MATERIALS: Data were analyzed from 128 prostate cancer patients treated with 3-dimensional conformal radiotherapy (3D-CRT) at The University of Texas M.D. Anderson Cancer Center (UTMDACC). The DVH for total rectal volume, including contents, was obtained for each patient from the treatment-planning system. A DWH was also computed, using the outer rectal contour plus an autogenerated inner contour that corresponds to an assumed 3-mm rectal wall thickness. The endpoint for analysis was Grade 2 or higher late rectal bleeding within 2 years of treatment; all patients had at least 2 years of follow-up. Four different NTCP models were fitted to the response data by using either the DVH or the DWH to describe the dose distribution to rectum or rectal wall, respectively. The 4 models considered were the Lyman model, the mean dose model, the parallel-architecture model, and a model based on the volume of a organ receiving more than a specified dose (the "cutoff-dose" model). RESULTS: For each of the models, the fit to the late rectal bleeding data was slightly improved when the analysis was based on the rectal DWH instead of on the DVH. In addition, the results of the cutoff dose and parallel architecture models were consistent with one another for the DWH data but not for the DVH data. For the DWH data, both models predict a 50% or higher incidence of Grade 2 or worse late rectal bleeding within 2 years if 80% or more of the rectal wall is exposed to doses greater than 32 Gy. A 50% or higher incidence of rectal bleeding is also predicted if the mean dose to rectal wall exceeds 53.2 Gy. CONCLUSIONS: A consistent, although modest, improvement occurs in the fits of NTCP models to the UTMDACC 2-year late rectal bleeding data when the fit is based on the rectal dose-wall histogram instead of on the dose-volume histogram for entire rectum, including contents.

Confidence Intervals↗

Development of methods for beam angle optimization for IMRT using an accelerated exhaustive search strategy.

PURPOSE: The purpose of this article is to explore the use of the accelerated exhaustive search strategy for developing and validating methods for optimizing beam orientations for intensity-modulated radiation therapy (IMRT). Combining beam-angle optimization (BAO) with intensity distribution optimization is expected to improve the quality of IMRT treatment plans. However, BAO is one of the most difficult problems to solve adequately because of the huge hyperspace of possible beam configurations (e.g., selecting 7 of 36 uniformly spaced coplanar beams would require the intercomparison of 8,347,680 IMRT plans). METHODS AND MATERIALS: An "influence vector" (IV) approximation technique for high-speed estimation of IMRT dose distributions was used in combination with a fast gradient search algorithm (Newton's method) for IMRT optimization. In the IV approximation, it is assumed that the change in intensity of a ray (or bixel) proportionately changes dose along the ray. Evidence is presented that the IV approximation is valid for BAO. The scatter contribution at points away from the ray is accounted for fully in IMRT optimization after the optimum beam orientation has been determined. IVs for all candidate beam angles are generated before the start of optimization. For all subsets of beams selected from a given pool of beams (e.g., 5 of 24 uniformly spaced beams), the distribution of planning scores for the best and the worst plans, optimum angle distributions, dose distributions, and dose-volume histograms (DVH) were analyzed for one prostate and two lung cancer cases. The results of the exhaustive search technique were used to develop a "multiresolution" search strategy. In this approach, a smaller number of beams (e.g., three) is first used to explore the hyperspace of solutions to determine the most preferred and the least preferred directions. The results of such exploration are then used as a starting point for determining an optimum configuration comprising a larger number of beams (e.g., seven). This two-step process is considerably faster than full exhaustive search. The question to be answered was whether the two methods lead to the same or similar solutions. The results of exhaustive search and multiresolution approaches were also compared with a previously published approach that used beam's-eye-view dosimetrics (BEVD). RESULTS: The relative ranks of plans optimized by an accurate dose calculation method were highly correlated with those of the plans optimized by the fast calculation method (i.e., using the IV approximation), which suggests that an approximate dose calculation algorithm can be used effectively for ranking of plans during BAO. We found that dose distributions and DVH of many beam configurations within a specified subset from a given pool of beams (e.g., 5 of 18) may be clinically indistinguishable and acceptable. Their optimized IMRT scores fall in a narrow range, although beam configurations and dose distributions may be different. We used the frequency distributions as a function of beam angles for the best 100 and the worst 100 plans to determine the most and the least preferred beam angles. We found that the most and the least preferred angle distributions for 3 of 18 configurations were very similar to those for 5, 6, 7, or 8 of 18 or 24 configurations, but the size of the search space was much smaller for the 3 of 18 case. Using fewer than three beams was discovered to be inadequate. This information was used to select the most preferred angles and eliminate the least preferred ones before searching for the optimum angles for the remaining beams. For the cases we studies, the multiresolution strategy produced very similar results to the full exhaustive search. Based on the observation that the worst plans had at least one parallel-opposed pair of beams and virtually all of the best plans had none, we were able to further reduce the size of the search space dramatically by using a pool of only nonparallel-opposed equispaced beams (i.e., 7 of 19 instead of 7 of 36). Another observation was that the probability of finding an optimum configuration in a smaller beam pool is substantially lower than in a larger pool (e.g., 5 of 18 vs. 5 of 24). The implication of this BAO is not very important when a large number of beams (nine or more) is used and vice versa. Our results showed that the plans with fewer but optimally placed beams could be as good as or better than plans using a larger number of unoptimized or uniformly placed beams. CONCLUSION: Exhaustive search with fast IMRT algorithms provides a novel and realistic approach to study the characteristics of IMRT dose distributions as a function of beam angles and to design practical BAO strategies for IMRT planning.

Algorithms↗