Many patients with non-small cell lung cancer (NSCLC) receive external beam radiation therapy as ... more Many patients with non-small cell lung cancer (NSCLC) receive external beam radiation therapy as part of their treatment. Three-dimensional conformal radiation therapy (3DCRT) commonly uses computed tomography (CT) to accurately delineate the target lesion and normal tissues. Clinical studies, however, indicate that positron emission tomography (PET) has higher sensitivity than CT in detecting and staging of mediastinal metastases. Imaging with fluoro-2-deoxyglucose (FDG) PET in conjunction with CT, therefore, can improve the accuracy of lesion definition. In this pilot study, we investigated the potential benefits of incorporating PET data into the conventional treatment planning of NSCLC. Case-by-case, we prospectively analyzed planning target volume (PTV) and lung toxicity changes for a cohort of patients. We have included 11 patients in this study. They were immobilized in the treatment position and CT simulation was performed. Following CT simulation, PET scanning was performed in the treatment position using the same body cast that was produced for CT simulation and treatment. The PTV, along with the gross target volume (GTV) and normal organs, was first delineated using the CT data set. The CT and PET transmission images were then registered in the treatment planning system using either manual or automated methods, leading to consequent registration of the CT and emission images. The PTV was then modified using the registered PET emission images. The modified PTV is seen simultaneously on both CT and PET images, allowing the physician to define the PTV utilizing the information from both data sets. Dose-volume histograms (DVHs) for lesion and normal organs were generated using both CT-based and PET+CT-based treatment plans. For all patients, there was a change in PTV outline based on CT images versus CT/PET fused images. In seven out of 11 cases, we found an increase in PTV volume (average increase of 19%) to incorporate distant nodal disease. Among these patients, the highest normal-tissue complication probability (NTCP) for lung was 22% with combined PET/CT plan and 21% with CT-only plan. In other four patients PTV was decreased an average of 18%. The reduction of PTV in two of these patients was due to excluding atelectasis and trimming the target volume to avoid delivering higher radiation doses to nearby spinal cord or heart. The incorporation of PET data improves definition of the primary lesion by including positive lymph nodes into the PTV. Thus, the PET data reduces the likelihood of geographic misses and hopefully improves the chance of achieving local control.
Proceedings of SPIE - The International Society for Optical Engineering
We investigated the use of MI to register images of the pelvis and thorax regions which is a comp... more We investigated the use of MI to register images of the pelvis and thorax regions which is a complex problem compared to the head since changes occur in soft tissue while the bony anatomy stays stable. We focused on the bony anatomy eliminating the soft tissue data by applying the MI for bone intensities. Instead of linear binning the whole spectrum of CT intensities, we bin the intensities chosen by the user as corresponding to the bone. We truncated the data spatially by choosing a region, because some bony anatomy might move from scan to scan relative to the stable parts i.e. ribs in the lung region might move with breathing or legs in the pelvis. We compare the effects of using our intensity-dependent- regional MI to the original MI for 9 pairs of CT-CT pelvis, 3 pairs of CT-CT lung and 5 pairs of CT-PET patient studies. With the original algorithm, the root-mean-square registration error can be as high 2 cm for CT-CT. The registration error with the intensity-dependent-regional...
A study was performed to correlate activity quantitation derived from external imaging with surgi... more A study was performed to correlate activity quantitation derived from external imaging with surgical tumor specimens in patients who received radiolabeled monoclonal antibody. Patients were given I-131 labeled 16.88 human antibody and scanned 3-5 times by planar and/or single photon emission computed tomography imaging methods to acquire time-dependent activity data in tumor and normal tissues. A method also was developed to assess the heterogeneous activity distributions in tumor samples. Postsurgical tumor and normal tissue samples were subdivided into volume elements (voxels) of 0.5 cm x 0.5 cm x 0.05 cm thick, which were used to verify the activity quantitation computed by the conjugate view method and to appraise the heterogeneity of radiolabeled antibody uptake. Through the use of the measured voxel activities, along with the time-dependent activity curves available for the entire tumor specimen derived from imaging, the cumulated activity and absorbed dose for each voxel were uniquely determined. The calculated total absorbed dose values were color-coded as isodose curves and overlaid on a correlated computed tomographic image. In two patients, activity quantitation derived from external imaging correlated with surgical tumor resection specimens within +/- 11%. The tumor-absorbed dose heterogeneity ratio was found to be as high as 10:1, with an average tumor to whole body absorbed dose ratio of 4:1. The mapping of activity with a histologic overlay showed a good correlation among activity uptake, the presence of tumor, and antigen expression on a microscopic scale. The resultant isodose curves overlaid on correlative computed tomographic scans represent the first images obtained with actual radiolabeled antibody biodistribution data in patients.
Proceedings of the 1992 International Biomedical Engineering Days, 1992
Extraction of stimulus evoked potentials (EP) out of the data recorded at the scalp is a difficul... more Extraction of stimulus evoked potentials (EP) out of the data recorded at the scalp is a difficult problem because of poor signal-to-noise ratio. Ensemble averaging techniques do not always give entirely satisfactory results because of signal variability, in terms of shape and latency variations . To cope with this signal variability many signal processing methods have been proposed. These include Wiener filtering and its extensions and recently, Neural Network signal processing techniques.
Proceedings of 16th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 2000
In radionuclide therapy, absorbed dose is calculated by convolution of a three-dimensional activi... more In radionuclide therapy, absorbed dose is calculated by convolution of a three-dimensional activity matrix with a three-dimensional dose point kernel. A technique employing the fast Hartley Transform (FHT) has been developed to perform this calculation. An important part of that development was the indexing scheme for 3D data. The results of this new FHT convolution technique were compared to direct convolution. A cube was convolved with itself by these two techniques. The results differed by less than 2 percent. In an effort to show the practical applicability of 3D convolution, a three-dimensional activity matrix from a I-131-labeled 16.88 monoclonal antibody patient was convolved with beta and photon dose point kernels using direct convolution. Isodose contours were then generated from the calculated absorbed dose matrix and overlaid on a CT image of the patient
Thresholding is the most widely used organ or tumor segmentation technique used in single photon ... more Thresholding is the most widely used organ or tumor segmentation technique used in single photon emission computed tomography (SPECT) and planar imaging for monoclonal antibodies. Selecting the optimal threshold requires a priori knowledge (volumes from CT or magnetic resonance) for the size and contrast level of the organ in question. Failure to select an optimal threshold leads to overestimation or underestimation of the volume and, subsequently, the organ-absorbed dose value in radio immunotherapy. To investigate this threshold selection problem, we per formed a phantom experiment using six lucite spheres ranging from 1 to 117 ml and filled with a uniform activity of 1 MCi/nilTc-99m. These spheres were placed at the center and off-center locations of a Jasczsak phantom and scanned with a three-headed gamma camera in SPECT and planar modes. Target:nontarget (T:NT) ratios were changed by adding the appropriate activity to the background. A threshold search algorithm with an interpolative background correction was applied to sphere ins ages. This algorithm selects a threshold that minimizes the difference between the true and measured volumes (SPECT) or areas (planar). It was found that for spheres equal to or larger than 20 ml [diameter (D) > 38 mm] and T:NT ratios higher than 5:1, mean thresholds at 42% for SPECT and 38% for planar imaging yielded minimum image segmentation errors, which is in agreement with current literature. However, for small T:NT ratios (<5:1), the threshold values as high as 71% for SPECT and 85% for planar imaging were substantially different than those fixed thresholds for large spheres (D > 38 mm). Hence, the use of fixed thresholds in low contrasts and with twnor and organ sizes of clinical interest (25 D @ 50 mm) may result in limited volume estimation accuracy. Therefore, we have provided the investigator a method to obtain the threshold values in which the proper threshold can be selected based on the organ and tumor size and image contrast. By measuring and calibrating the proper thresh old value derived through machine-specific phantom measurements, a more accurate volume and activity quantitation can be performed. This, in turn, will provide tumor-absorbed dose optimization and greater ac curacy in the measurement of potentially subacute, toxic absorbed doses to normal organs for patients undergoing radioimmunotherapy.
International Journal of Radiation Oncology*Biology*Physics, 2008
Purpose/Objective(s): The treatment of MPM after pleurectomy/decortication (P/D) remains a therap... more Purpose/Objective(s): The treatment of MPM after pleurectomy/decortication (P/D) remains a therapeutic challenge. A recent report showed poor local control and long term survival with traditional mixed photon/electron treatment. Tumor delineation in these situations is also challenging due to the difficulty in distinguishing tumor from non-malignant radiographic abnormalities. Therefore, we have incorporated registered 18-FDG -PET scans as part of the treatment planning process. This study reports on changes in treatment volumes with the use of the PET images. Materials/Methods: Eleven patients with malignant pleural mesothelioma who underwent pleurectomy/decortication or were unresectable were enrolled in a prospective IRB-approved feasibility study. These patients were not candidates for extrapleural pneumonectomy due to impaired pulmonary function or extent of tumor. An 18-FDG-PET was performed at the time of simulation in the treatment position and registered with the treatment planning CT to aid in tumor delineation. Two planning target volumes (PTV) were delineated: a CT-only PTV and a CT/PET PTV. All treatment plans were with intensity modulated radiation therapy. Results: All PTVs are large (average ± SD CT/PET PTV is 2,108 ± 746 cc). In all patients, the planning target volume was modified by the information from the PET scan. The average ratio of the CT-only to the CT/PET PTV was 95% (range 75.7%-107.3%, SD 7.7%). In nine cases, the PTV volume increased with the addition of PET as compared to CT only. In all cases, a portion of the CT-only PTV was not included in the CT/PET PTV. The average ± SD of the ratio of the volume included in both PTVs to the volume of the CT/PET PTV was 91.7% ± 7.1% (range 72%-97.3%). Preliminary results show that underdose metrics for the CT/PET PTV can be strongly reduced if the treatment plan is designed to cover the CT-only PTV, ignoring regions added by the PET study. In one case, the plan designed to give 50.4 Gy to 95% of the CT/PET PTV gave minimum dose to the CT/PET PTV of 41.6 Gy while the plan designed to give 50.4 Gy to the CT-only PTV gave minimum dose to the CT/PET PTV of 4.8 Gy, with 25 cc receiving below 41.6 Gy. Conclusions: The use of 18-FDG-PET for tumor delineation is feasible and changes PTV delineation in most cases of mesothelioma that have not undergone pneumonectomy. We have opened a Phase II study of chemotherapy and IMRT in patients with unresectable MPM using 18-FDG-PET in the treatment planning process.
A study was performed to correlate activity quantitation derived from external imaging with surgi... more A study was performed to correlate activity quantitation derived from external imaging with surgical tumor specimens in patients who received radiolabeled monoclonal antibody. Patients were given I-131 labeled 16.88 human antibody and scanned 3-5 times by planar and/or single photon emission computed tomography imaging methods to acquire time-dependent activity data in tumor and normal tissues. A method also was developed to assess the heterogeneous activity distributions in tumor samples. Postsurgical tumor and normal tissue samples were subdivided into volume elements (voxels) of 0.5 cm x 0.5 cm x 0.05 cm thick, which were used to verify the activity quantitation computed by the conjugate view method and to appraise the heterogeneity of radiolabeled antibody uptake. Through the use of the measured voxel activities, along with the time-dependent activity curves available for the entire tumor specimen derived from imaging, the cumulated activity and absorbed dose for each voxel were uniquely determined. The calculated total absorbed dose values were color-coded as isodose curves and overlaid on a correlated computed tomographic image. In two patients, activity quantitation derived from external imaging correlated with surgical tumor resection specimens within +/- 11%. The tumor-absorbed dose heterogeneity ratio was found to be as high as 10:1, with an average tumor to whole body absorbed dose ratio of 4:1. The mapping of activity with a histologic overlay showed a good correlation among activity uptake, the presence of tumor, and antigen expression on a microscopic scale. The resultant isodose curves overlaid on correlative computed tomographic scans represent the first images obtained with actual radiolabeled antibody biodistribution data in patients.
The use of computed tomography (CT) or magnetic resonance (MR) to overlay or register uptake patt... more The use of computed tomography (CT) or magnetic resonance (MR) to overlay or register uptake patterns displayed by single-photon emission computed tomography (SPECT) with specific underlying anatomy has the potential to improve image interpretation and decrease diagnostic reading errors. The authors have developed a method that will allow the selection of a region of interest on MR or CT images that correlates with SPECT antibody images from the same patient. This method was validated first in phantom studies and subsequently was used on three patients with suspected colorectal carcinoma. Two patients were injected with the technetium-99m-labeled 88BV59 immunoglobulin G human antibody, and the third patient was injected with the iodine-131-labeled 16.88 immunoglobulin M human antibody. CT or MR scans were obtained before antibody infusion, and subsequent SPECT scans were obtained on the first or fourth day after infusion. A customized body cast with landmarks was used for each patient during the CT, MR, and SPECT scans to match slice positions for all scanning modalities. Corresponding fiducial landmarks were identified on axial images. A computer graphics program was written to match and overlay corresponding landmarks for each imaging modality. The image registration accuracy was measured by comparing fiducial marker separations (center to center) on the registered scans. This separation uncertainty was 1-2 mm for CT-MR and 3-4 mm for CT-SPECT phantom studies. For patient studies, the fiducial alignment uncertainty was 3-4 mm for axial CT-SPECT and MR-SPECT images, and 6-8 mm for sagittal CT-SPECT and MR-SPECT images. The accuracy of the anatomic alignment of the patient and image registration system was +/- 1 cm in the medial-lateral axis and +/- 2 cm in the cranial-caudal direction. This type of image analysis may resolve uncertainties with the anatomic correlation of SPECT images that otherwise may be regarded as questionable when SPECT is used alone for radioimmunodiagnosis.
Proceedings of 16th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 1994
A median filtered pyramidal multiresolution (MFPM) image segmentation method for detecting and de... more A median filtered pyramidal multiresolution (MFPM) image segmentation method for detecting and delineating compact objects was applied to single-photon emission computed tomography (SPECT) images. These SPECT images were obtained by scanning spheres from 1 to 54 ml in size and from 50% to 100% contrast settings. The algorithm performed accurately for large sphere (20 and 54 ml) and high contrast (90% and 100%) cases. As the size and contrast decrease, the accuracy of the method also decreases. Comparison of the MFPM method with adaptive thresholding with edge-preserving smoothing (ATEPS) indicated superior performance of the MFPM method
The goal for this work was to develop a method to determine the feasibility of estimating absorbe... more The goal for this work was to develop a method to determine the feasibility of estimating absorbed dose distribution of I-131 thyroid therapy using I-124 PET images of residual thyroid lesions with the dose constraint of 200 cGy to blood, that is a surrogate for bone marrow toxicity. A dose response study has been carried out on 3 patients with papillary thyroid carcinoma. Those patients were given 15-37 MBq of I-124 along with 74-185 MBq of I-131. PET imaging was performed 2-4 hour and then at 24 hour and either 48 hour, or 72 hour post-infusion. Lesion masses were computed from PET images using an adaptive thresholding technique. The definition of the boundary enabled determination of the iodine activity within the lesion. Time-activity curves were fitted to estimate the cumulated activity and therefore the absorbed dose per MBq administered. Daily blood and total body counts were performed on the patients using a multichannel analyzer with windows set for both I-131 (364 keV) and I-124 (511 keV). Cross-talk corrections from one isotope into the alternate window was determined using a standard of each respective isotope. At maximum-tolerated-activity (MTA) that delivers 200 cGy radiation dose to the blood, the dose to lesions from I-131 varied from 0.04 to 2.44 cGy/MBq (1.57-90.48 rads/mCi) with effective half-lives for I-124 ranging from 0.58 to 1.86 days. The three-dimensional absorbed dose distribution in the thyroid lesions was calculated by convolving the activity values with an I-131 point-source kernel using a Fast Hartley Transform. The calculated mean absorbed dose distribution was displayed as isodose lines on PET images that can be used to refine the amount of administered activity. PET with I-124 may improve the absorbed dose estimates from radioiodine therapy with I-131 in the treatment of thyroid cancer. The capability of estimating I-131 mean absorbed dose distributions from serial I-124 PET images can lead to patient-specific treatment planning for thyroid therapy. (Clin Pos Imag 1999;2:41-46)
The objective of this work was to develop and then validate a stereotactic fiduciary marker syste... more The objective of this work was to develop and then validate a stereotactic fiduciary marker system for tumor xenografts in rodents which could be used to co-register magnetic resonance imaging (MRI), PET, tissue histology, autoradiography, and measurements from physiologic probes. A Teflon fiduciary template has been designed which allows the precise insertion of small hollow Teflon rods (0.71 mm diameter) into a tumor. These rods can be visualized by MRI and PET as well as by histology and autoradiography on tissue sections. The methodology has been applied and tested on a rigid phantom, on tissue phantom material, and finally on tumor bearing mice. Image registration has been performed between the MRI and PET images for the rigid Teflon phantom and among MRI, digitized microscopy images of tissue histology, and autoradiograms for both tissue phantom and tumor-bearing mice. A registration accuracy, expressed as the average Euclidean distance between the centers of three fiduciary markers among the registered image sets, of 0.2 +/- 0.06 mm was achieved between MRI and microPET image sets of a rigid Teflon phantom. The fiduciary template allows digitized tissue sections to be co-registered with three-dimensional MRI images with an average accuracy of 0.21 and 0.25 mm for the tissue phantoms and tumor xenografts, respectively. Between histology and autoradiograms, it was 0.19 and 0.21 mm for tissue phantoms and tumor xenografts, respectively. The fiduciary marker system provides a coordinate system with which to correlate information from multiple image types, on a voxel-by-voxel basis, with sub-millimeter accuracy--even among imaging modalities with widely disparate spatial resolution and in the absence of identifiable anatomic landmarks.
International Journal of Radiation Oncology*Biology*Physics, 2000
Purpose/Objective(s): The treatment of MPM after pleurectomy/decortication (P/D) remains a therap... more Purpose/Objective(s): The treatment of MPM after pleurectomy/decortication (P/D) remains a therapeutic challenge. A recent report showed poor local control and long term survival with traditional mixed photon/electron treatment. Tumor delineation in these situations is also challenging due to the difficulty in distinguishing tumor from non-malignant radiographic abnormalities. Therefore, we have incorporated registered 18-FDG -PET scans as part of the treatment planning process. This study reports on changes in treatment volumes with the use of the PET images. Materials/Methods: Eleven patients with malignant pleural mesothelioma who underwent pleurectomy/decortication or were unresectable were enrolled in a prospective IRB-approved feasibility study. These patients were not candidates for extrapleural pneumonectomy due to impaired pulmonary function or extent of tumor. An 18-FDG-PET was performed at the time of simulation in the treatment position and registered with the treatment planning CT to aid in tumor delineation. Two planning target volumes (PTV) were delineated: a CT-only PTV and a CT/PET PTV. All treatment plans were with intensity modulated radiation therapy. Results: All PTVs are large (average ± SD CT/PET PTV is 2,108 ± 746 cc). In all patients, the planning target volume was modified by the information from the PET scan. The average ratio of the CT-only to the CT/PET PTV was 95% (range 75.7%-107.3%, SD 7.7%). In nine cases, the PTV volume increased with the addition of PET as compared to CT only. In all cases, a portion of the CT-only PTV was not included in the CT/PET PTV. The average ± SD of the ratio of the volume included in both PTVs to the volume of the CT/PET PTV was 91.7% ± 7.1% (range 72%-97.3%). Preliminary results show that underdose metrics for the CT/PET PTV can be strongly reduced if the treatment plan is designed to cover the CT-only PTV, ignoring regions added by the PET study. In one case, the plan designed to give 50.4 Gy to 95% of the CT/PET PTV gave minimum dose to the CT/PET PTV of 41.6 Gy while the plan designed to give 50.4 Gy to the CT-only PTV gave minimum dose to the CT/PET PTV of 4.8 Gy, with 25 cc receiving below 41.6 Gy. Conclusions: The use of 18-FDG-PET for tumor delineation is feasible and changes PTV delineation in most cases of mesothelioma that have not undergone pneumonectomy. We have opened a Phase II study of chemotherapy and IMRT in patients with unresectable MPM using 18-FDG-PET in the treatment planning process.
European Journal of Nuclear Medicine and Molecular Imaging, 2000
. Approximately 170,000 people arediagnosed with lung cancer in the United States each year. Ma... more . Approximately 170,000 people arediagnosed with lung cancer in the United States each year. Manyof these patients receive external beam radiation for treatment. Fluorine-18 2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG PET) is increasingly being used in evaluating non-small cell lung cancer and may be of clinical utility in assessing response to treatment. In this report, we present FDG PET images and
tions to voxel dosimetry: the voxel S value approach based on the MIRD schema. Examples are provi... more tions to voxel dosimetry: the voxel S value approach based on the MIRD schema. Examples are provided wherein voxel S values are applied to nonuniform activity distributions to assess isodose contours and dose-volume histograms (DVHs) within treated tissue regions. Extensions of the approach are applied to autoradiographic data on radiopharmaceutical localization. The potential of these techniques to attain improved correlations with biologic response is also discussed.
Many patients with non-small cell lung cancer (NSCLC) receive external beam radiation therapy as ... more Many patients with non-small cell lung cancer (NSCLC) receive external beam radiation therapy as part of their treatment. Three-dimensional conformal radiation therapy (3DCRT) commonly uses computed tomography (CT) to accurately delineate the target lesion and normal tissues. Clinical studies, however, indicate that positron emission tomography (PET) has higher sensitivity than CT in detecting and staging of mediastinal metastases. Imaging with fluoro-2-deoxyglucose (FDG) PET in conjunction with CT, therefore, can improve the accuracy of lesion definition. In this pilot study, we investigated the potential benefits of incorporating PET data into the conventional treatment planning of NSCLC. Case-by-case, we prospectively analyzed planning target volume (PTV) and lung toxicity changes for a cohort of patients. We have included 11 patients in this study. They were immobilized in the treatment position and CT simulation was performed. Following CT simulation, PET scanning was performed in the treatment position using the same body cast that was produced for CT simulation and treatment. The PTV, along with the gross target volume (GTV) and normal organs, was first delineated using the CT data set. The CT and PET transmission images were then registered in the treatment planning system using either manual or automated methods, leading to consequent registration of the CT and emission images. The PTV was then modified using the registered PET emission images. The modified PTV is seen simultaneously on both CT and PET images, allowing the physician to define the PTV utilizing the information from both data sets. Dose-volume histograms (DVHs) for lesion and normal organs were generated using both CT-based and PET+CT-based treatment plans. For all patients, there was a change in PTV outline based on CT images versus CT/PET fused images. In seven out of 11 cases, we found an increase in PTV volume (average increase of 19%) to incorporate distant nodal disease. Among these patients, the highest normal-tissue complication probability (NTCP) for lung was 22% with combined PET/CT plan and 21% with CT-only plan. In other four patients PTV was decreased an average of 18%. The reduction of PTV in two of these patients was due to excluding atelectasis and trimming the target volume to avoid delivering higher radiation doses to nearby spinal cord or heart. The incorporation of PET data improves definition of the primary lesion by including positive lymph nodes into the PTV. Thus, the PET data reduces the likelihood of geographic misses and hopefully improves the chance of achieving local control.
Proceedings of SPIE - The International Society for Optical Engineering
We investigated the use of MI to register images of the pelvis and thorax regions which is a comp... more We investigated the use of MI to register images of the pelvis and thorax regions which is a complex problem compared to the head since changes occur in soft tissue while the bony anatomy stays stable. We focused on the bony anatomy eliminating the soft tissue data by applying the MI for bone intensities. Instead of linear binning the whole spectrum of CT intensities, we bin the intensities chosen by the user as corresponding to the bone. We truncated the data spatially by choosing a region, because some bony anatomy might move from scan to scan relative to the stable parts i.e. ribs in the lung region might move with breathing or legs in the pelvis. We compare the effects of using our intensity-dependent- regional MI to the original MI for 9 pairs of CT-CT pelvis, 3 pairs of CT-CT lung and 5 pairs of CT-PET patient studies. With the original algorithm, the root-mean-square registration error can be as high 2 cm for CT-CT. The registration error with the intensity-dependent-regional...
A study was performed to correlate activity quantitation derived from external imaging with surgi... more A study was performed to correlate activity quantitation derived from external imaging with surgical tumor specimens in patients who received radiolabeled monoclonal antibody. Patients were given I-131 labeled 16.88 human antibody and scanned 3-5 times by planar and/or single photon emission computed tomography imaging methods to acquire time-dependent activity data in tumor and normal tissues. A method also was developed to assess the heterogeneous activity distributions in tumor samples. Postsurgical tumor and normal tissue samples were subdivided into volume elements (voxels) of 0.5 cm x 0.5 cm x 0.05 cm thick, which were used to verify the activity quantitation computed by the conjugate view method and to appraise the heterogeneity of radiolabeled antibody uptake. Through the use of the measured voxel activities, along with the time-dependent activity curves available for the entire tumor specimen derived from imaging, the cumulated activity and absorbed dose for each voxel were uniquely determined. The calculated total absorbed dose values were color-coded as isodose curves and overlaid on a correlated computed tomographic image. In two patients, activity quantitation derived from external imaging correlated with surgical tumor resection specimens within +/- 11%. The tumor-absorbed dose heterogeneity ratio was found to be as high as 10:1, with an average tumor to whole body absorbed dose ratio of 4:1. The mapping of activity with a histologic overlay showed a good correlation among activity uptake, the presence of tumor, and antigen expression on a microscopic scale. The resultant isodose curves overlaid on correlative computed tomographic scans represent the first images obtained with actual radiolabeled antibody biodistribution data in patients.
Proceedings of the 1992 International Biomedical Engineering Days, 1992
Extraction of stimulus evoked potentials (EP) out of the data recorded at the scalp is a difficul... more Extraction of stimulus evoked potentials (EP) out of the data recorded at the scalp is a difficult problem because of poor signal-to-noise ratio. Ensemble averaging techniques do not always give entirely satisfactory results because of signal variability, in terms of shape and latency variations . To cope with this signal variability many signal processing methods have been proposed. These include Wiener filtering and its extensions and recently, Neural Network signal processing techniques.
Proceedings of 16th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 2000
In radionuclide therapy, absorbed dose is calculated by convolution of a three-dimensional activi... more In radionuclide therapy, absorbed dose is calculated by convolution of a three-dimensional activity matrix with a three-dimensional dose point kernel. A technique employing the fast Hartley Transform (FHT) has been developed to perform this calculation. An important part of that development was the indexing scheme for 3D data. The results of this new FHT convolution technique were compared to direct convolution. A cube was convolved with itself by these two techniques. The results differed by less than 2 percent. In an effort to show the practical applicability of 3D convolution, a three-dimensional activity matrix from a I-131-labeled 16.88 monoclonal antibody patient was convolved with beta and photon dose point kernels using direct convolution. Isodose contours were then generated from the calculated absorbed dose matrix and overlaid on a CT image of the patient
Thresholding is the most widely used organ or tumor segmentation technique used in single photon ... more Thresholding is the most widely used organ or tumor segmentation technique used in single photon emission computed tomography (SPECT) and planar imaging for monoclonal antibodies. Selecting the optimal threshold requires a priori knowledge (volumes from CT or magnetic resonance) for the size and contrast level of the organ in question. Failure to select an optimal threshold leads to overestimation or underestimation of the volume and, subsequently, the organ-absorbed dose value in radio immunotherapy. To investigate this threshold selection problem, we per formed a phantom experiment using six lucite spheres ranging from 1 to 117 ml and filled with a uniform activity of 1 MCi/nilTc-99m. These spheres were placed at the center and off-center locations of a Jasczsak phantom and scanned with a three-headed gamma camera in SPECT and planar modes. Target:nontarget (T:NT) ratios were changed by adding the appropriate activity to the background. A threshold search algorithm with an interpolative background correction was applied to sphere ins ages. This algorithm selects a threshold that minimizes the difference between the true and measured volumes (SPECT) or areas (planar). It was found that for spheres equal to or larger than 20 ml [diameter (D) > 38 mm] and T:NT ratios higher than 5:1, mean thresholds at 42% for SPECT and 38% for planar imaging yielded minimum image segmentation errors, which is in agreement with current literature. However, for small T:NT ratios (<5:1), the threshold values as high as 71% for SPECT and 85% for planar imaging were substantially different than those fixed thresholds for large spheres (D > 38 mm). Hence, the use of fixed thresholds in low contrasts and with twnor and organ sizes of clinical interest (25 D @ 50 mm) may result in limited volume estimation accuracy. Therefore, we have provided the investigator a method to obtain the threshold values in which the proper threshold can be selected based on the organ and tumor size and image contrast. By measuring and calibrating the proper thresh old value derived through machine-specific phantom measurements, a more accurate volume and activity quantitation can be performed. This, in turn, will provide tumor-absorbed dose optimization and greater ac curacy in the measurement of potentially subacute, toxic absorbed doses to normal organs for patients undergoing radioimmunotherapy.
International Journal of Radiation Oncology*Biology*Physics, 2008
Purpose/Objective(s): The treatment of MPM after pleurectomy/decortication (P/D) remains a therap... more Purpose/Objective(s): The treatment of MPM after pleurectomy/decortication (P/D) remains a therapeutic challenge. A recent report showed poor local control and long term survival with traditional mixed photon/electron treatment. Tumor delineation in these situations is also challenging due to the difficulty in distinguishing tumor from non-malignant radiographic abnormalities. Therefore, we have incorporated registered 18-FDG -PET scans as part of the treatment planning process. This study reports on changes in treatment volumes with the use of the PET images. Materials/Methods: Eleven patients with malignant pleural mesothelioma who underwent pleurectomy/decortication or were unresectable were enrolled in a prospective IRB-approved feasibility study. These patients were not candidates for extrapleural pneumonectomy due to impaired pulmonary function or extent of tumor. An 18-FDG-PET was performed at the time of simulation in the treatment position and registered with the treatment planning CT to aid in tumor delineation. Two planning target volumes (PTV) were delineated: a CT-only PTV and a CT/PET PTV. All treatment plans were with intensity modulated radiation therapy. Results: All PTVs are large (average ± SD CT/PET PTV is 2,108 ± 746 cc). In all patients, the planning target volume was modified by the information from the PET scan. The average ratio of the CT-only to the CT/PET PTV was 95% (range 75.7%-107.3%, SD 7.7%). In nine cases, the PTV volume increased with the addition of PET as compared to CT only. In all cases, a portion of the CT-only PTV was not included in the CT/PET PTV. The average ± SD of the ratio of the volume included in both PTVs to the volume of the CT/PET PTV was 91.7% ± 7.1% (range 72%-97.3%). Preliminary results show that underdose metrics for the CT/PET PTV can be strongly reduced if the treatment plan is designed to cover the CT-only PTV, ignoring regions added by the PET study. In one case, the plan designed to give 50.4 Gy to 95% of the CT/PET PTV gave minimum dose to the CT/PET PTV of 41.6 Gy while the plan designed to give 50.4 Gy to the CT-only PTV gave minimum dose to the CT/PET PTV of 4.8 Gy, with 25 cc receiving below 41.6 Gy. Conclusions: The use of 18-FDG-PET for tumor delineation is feasible and changes PTV delineation in most cases of mesothelioma that have not undergone pneumonectomy. We have opened a Phase II study of chemotherapy and IMRT in patients with unresectable MPM using 18-FDG-PET in the treatment planning process.
A study was performed to correlate activity quantitation derived from external imaging with surgi... more A study was performed to correlate activity quantitation derived from external imaging with surgical tumor specimens in patients who received radiolabeled monoclonal antibody. Patients were given I-131 labeled 16.88 human antibody and scanned 3-5 times by planar and/or single photon emission computed tomography imaging methods to acquire time-dependent activity data in tumor and normal tissues. A method also was developed to assess the heterogeneous activity distributions in tumor samples. Postsurgical tumor and normal tissue samples were subdivided into volume elements (voxels) of 0.5 cm x 0.5 cm x 0.05 cm thick, which were used to verify the activity quantitation computed by the conjugate view method and to appraise the heterogeneity of radiolabeled antibody uptake. Through the use of the measured voxel activities, along with the time-dependent activity curves available for the entire tumor specimen derived from imaging, the cumulated activity and absorbed dose for each voxel were uniquely determined. The calculated total absorbed dose values were color-coded as isodose curves and overlaid on a correlated computed tomographic image. In two patients, activity quantitation derived from external imaging correlated with surgical tumor resection specimens within +/- 11%. The tumor-absorbed dose heterogeneity ratio was found to be as high as 10:1, with an average tumor to whole body absorbed dose ratio of 4:1. The mapping of activity with a histologic overlay showed a good correlation among activity uptake, the presence of tumor, and antigen expression on a microscopic scale. The resultant isodose curves overlaid on correlative computed tomographic scans represent the first images obtained with actual radiolabeled antibody biodistribution data in patients.
The use of computed tomography (CT) or magnetic resonance (MR) to overlay or register uptake patt... more The use of computed tomography (CT) or magnetic resonance (MR) to overlay or register uptake patterns displayed by single-photon emission computed tomography (SPECT) with specific underlying anatomy has the potential to improve image interpretation and decrease diagnostic reading errors. The authors have developed a method that will allow the selection of a region of interest on MR or CT images that correlates with SPECT antibody images from the same patient. This method was validated first in phantom studies and subsequently was used on three patients with suspected colorectal carcinoma. Two patients were injected with the technetium-99m-labeled 88BV59 immunoglobulin G human antibody, and the third patient was injected with the iodine-131-labeled 16.88 immunoglobulin M human antibody. CT or MR scans were obtained before antibody infusion, and subsequent SPECT scans were obtained on the first or fourth day after infusion. A customized body cast with landmarks was used for each patient during the CT, MR, and SPECT scans to match slice positions for all scanning modalities. Corresponding fiducial landmarks were identified on axial images. A computer graphics program was written to match and overlay corresponding landmarks for each imaging modality. The image registration accuracy was measured by comparing fiducial marker separations (center to center) on the registered scans. This separation uncertainty was 1-2 mm for CT-MR and 3-4 mm for CT-SPECT phantom studies. For patient studies, the fiducial alignment uncertainty was 3-4 mm for axial CT-SPECT and MR-SPECT images, and 6-8 mm for sagittal CT-SPECT and MR-SPECT images. The accuracy of the anatomic alignment of the patient and image registration system was +/- 1 cm in the medial-lateral axis and +/- 2 cm in the cranial-caudal direction. This type of image analysis may resolve uncertainties with the anatomic correlation of SPECT images that otherwise may be regarded as questionable when SPECT is used alone for radioimmunodiagnosis.
Proceedings of 16th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 1994
A median filtered pyramidal multiresolution (MFPM) image segmentation method for detecting and de... more A median filtered pyramidal multiresolution (MFPM) image segmentation method for detecting and delineating compact objects was applied to single-photon emission computed tomography (SPECT) images. These SPECT images were obtained by scanning spheres from 1 to 54 ml in size and from 50% to 100% contrast settings. The algorithm performed accurately for large sphere (20 and 54 ml) and high contrast (90% and 100%) cases. As the size and contrast decrease, the accuracy of the method also decreases. Comparison of the MFPM method with adaptive thresholding with edge-preserving smoothing (ATEPS) indicated superior performance of the MFPM method
The goal for this work was to develop a method to determine the feasibility of estimating absorbe... more The goal for this work was to develop a method to determine the feasibility of estimating absorbed dose distribution of I-131 thyroid therapy using I-124 PET images of residual thyroid lesions with the dose constraint of 200 cGy to blood, that is a surrogate for bone marrow toxicity. A dose response study has been carried out on 3 patients with papillary thyroid carcinoma. Those patients were given 15-37 MBq of I-124 along with 74-185 MBq of I-131. PET imaging was performed 2-4 hour and then at 24 hour and either 48 hour, or 72 hour post-infusion. Lesion masses were computed from PET images using an adaptive thresholding technique. The definition of the boundary enabled determination of the iodine activity within the lesion. Time-activity curves were fitted to estimate the cumulated activity and therefore the absorbed dose per MBq administered. Daily blood and total body counts were performed on the patients using a multichannel analyzer with windows set for both I-131 (364 keV) and I-124 (511 keV). Cross-talk corrections from one isotope into the alternate window was determined using a standard of each respective isotope. At maximum-tolerated-activity (MTA) that delivers 200 cGy radiation dose to the blood, the dose to lesions from I-131 varied from 0.04 to 2.44 cGy/MBq (1.57-90.48 rads/mCi) with effective half-lives for I-124 ranging from 0.58 to 1.86 days. The three-dimensional absorbed dose distribution in the thyroid lesions was calculated by convolving the activity values with an I-131 point-source kernel using a Fast Hartley Transform. The calculated mean absorbed dose distribution was displayed as isodose lines on PET images that can be used to refine the amount of administered activity. PET with I-124 may improve the absorbed dose estimates from radioiodine therapy with I-131 in the treatment of thyroid cancer. The capability of estimating I-131 mean absorbed dose distributions from serial I-124 PET images can lead to patient-specific treatment planning for thyroid therapy. (Clin Pos Imag 1999;2:41-46)
The objective of this work was to develop and then validate a stereotactic fiduciary marker syste... more The objective of this work was to develop and then validate a stereotactic fiduciary marker system for tumor xenografts in rodents which could be used to co-register magnetic resonance imaging (MRI), PET, tissue histology, autoradiography, and measurements from physiologic probes. A Teflon fiduciary template has been designed which allows the precise insertion of small hollow Teflon rods (0.71 mm diameter) into a tumor. These rods can be visualized by MRI and PET as well as by histology and autoradiography on tissue sections. The methodology has been applied and tested on a rigid phantom, on tissue phantom material, and finally on tumor bearing mice. Image registration has been performed between the MRI and PET images for the rigid Teflon phantom and among MRI, digitized microscopy images of tissue histology, and autoradiograms for both tissue phantom and tumor-bearing mice. A registration accuracy, expressed as the average Euclidean distance between the centers of three fiduciary markers among the registered image sets, of 0.2 +/- 0.06 mm was achieved between MRI and microPET image sets of a rigid Teflon phantom. The fiduciary template allows digitized tissue sections to be co-registered with three-dimensional MRI images with an average accuracy of 0.21 and 0.25 mm for the tissue phantoms and tumor xenografts, respectively. Between histology and autoradiograms, it was 0.19 and 0.21 mm for tissue phantoms and tumor xenografts, respectively. The fiduciary marker system provides a coordinate system with which to correlate information from multiple image types, on a voxel-by-voxel basis, with sub-millimeter accuracy--even among imaging modalities with widely disparate spatial resolution and in the absence of identifiable anatomic landmarks.
International Journal of Radiation Oncology*Biology*Physics, 2000
Purpose/Objective(s): The treatment of MPM after pleurectomy/decortication (P/D) remains a therap... more Purpose/Objective(s): The treatment of MPM after pleurectomy/decortication (P/D) remains a therapeutic challenge. A recent report showed poor local control and long term survival with traditional mixed photon/electron treatment. Tumor delineation in these situations is also challenging due to the difficulty in distinguishing tumor from non-malignant radiographic abnormalities. Therefore, we have incorporated registered 18-FDG -PET scans as part of the treatment planning process. This study reports on changes in treatment volumes with the use of the PET images. Materials/Methods: Eleven patients with malignant pleural mesothelioma who underwent pleurectomy/decortication or were unresectable were enrolled in a prospective IRB-approved feasibility study. These patients were not candidates for extrapleural pneumonectomy due to impaired pulmonary function or extent of tumor. An 18-FDG-PET was performed at the time of simulation in the treatment position and registered with the treatment planning CT to aid in tumor delineation. Two planning target volumes (PTV) were delineated: a CT-only PTV and a CT/PET PTV. All treatment plans were with intensity modulated radiation therapy. Results: All PTVs are large (average ± SD CT/PET PTV is 2,108 ± 746 cc). In all patients, the planning target volume was modified by the information from the PET scan. The average ratio of the CT-only to the CT/PET PTV was 95% (range 75.7%-107.3%, SD 7.7%). In nine cases, the PTV volume increased with the addition of PET as compared to CT only. In all cases, a portion of the CT-only PTV was not included in the CT/PET PTV. The average ± SD of the ratio of the volume included in both PTVs to the volume of the CT/PET PTV was 91.7% ± 7.1% (range 72%-97.3%). Preliminary results show that underdose metrics for the CT/PET PTV can be strongly reduced if the treatment plan is designed to cover the CT-only PTV, ignoring regions added by the PET study. In one case, the plan designed to give 50.4 Gy to 95% of the CT/PET PTV gave minimum dose to the CT/PET PTV of 41.6 Gy while the plan designed to give 50.4 Gy to the CT-only PTV gave minimum dose to the CT/PET PTV of 4.8 Gy, with 25 cc receiving below 41.6 Gy. Conclusions: The use of 18-FDG-PET for tumor delineation is feasible and changes PTV delineation in most cases of mesothelioma that have not undergone pneumonectomy. We have opened a Phase II study of chemotherapy and IMRT in patients with unresectable MPM using 18-FDG-PET in the treatment planning process.
European Journal of Nuclear Medicine and Molecular Imaging, 2000
. Approximately 170,000 people arediagnosed with lung cancer in the United States each year. Ma... more . Approximately 170,000 people arediagnosed with lung cancer in the United States each year. Manyof these patients receive external beam radiation for treatment. Fluorine-18 2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG PET) is increasingly being used in evaluating non-small cell lung cancer and may be of clinical utility in assessing response to treatment. In this report, we present FDG PET images and
tions to voxel dosimetry: the voxel S value approach based on the MIRD schema. Examples are provi... more tions to voxel dosimetry: the voxel S value approach based on the MIRD schema. Examples are provided wherein voxel S values are applied to nonuniform activity distributions to assess isodose contours and dose-volume histograms (DVHs) within treated tissue regions. Extensions of the approach are applied to autoradiographic data on radiopharmaceutical localization. The potential of these techniques to attain improved correlations with biologic response is also discussed.
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Papers by Alev Erdi