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Biomedical subjects

L J Boersma

Publications and source records attributed to L J Boersma.

At least 19 recordsLinked to original sources
PubMed2001

Paradoxical effects of trichostatin A: inhibition of NF-Y-associated histone acetyltransferase activity, phosphorylation of hGCN5 and downregulation of cyclin A and B1 mRNA.

Trichostatin A (TSA), an inhibitor of histone deacetylase (HDAC), is widely used to study the role of histone acetylation in gene expression, since genes that use histone acetylation as a means of regulating expression may be up regulated when TSA is added. In this study, however, we show that TSA has an unexpected paradoxical effect leading to inhibition of NF-Y-associated histone acetyl transferase (HAT) activity and phosphorylation of the HAT, hGCN5. TSA treatment of cells resulted in diminished levels of NF-Y-associated HAT activity without changes in NF-Y(A) amount. hGCN5 is one of the HATs known to associate with NF-Y. The association of hGCN5 with NF-Y was not altered by TSA treatment. The enzymatic activity of hGCN5 is known to be inhibited by phosphorylation. TSA treatment of Hela cells resulted in phosphorylation of hGCN5. Exposure of the NF-Y immunoprecipitates from TSA-treated cells to a phosphatase resulted in enhanced HAT activity. We have also shown that the mRNA levels of several genes, cyclin B1 and cyclin A, are downregulated by TSA; these effects do not require protein synthesis and the downregulation of cyclin B1 by TSA occurs through transcription. These results suggest that TSA can have contradictory effects, on one hand stimulating HAT activity in general by inhibition of HDACs, but also resulting in inhibition of NF-Y-associated HAT activity and phosphorylation of hGCN5.

Acetyltransferases↗
PubMed2000

Changes in local pulmonary injury up to 48 months after irradiation for lymphoma and breast cancer.

PURPOSE: To assess the recovery from early local pulmonary injury after irradiation and to determine whether regional differences exist. METHODS: For 110 patients treated for breast cancer or malignant lymphoma, single photon emission computed tomography (SPECT) perfusion and ventilation scans and CT scans were made before, 3, 18, and 48 months after radiotherapy. Dose-effect relations for changes in local perfusion, ventilation, and density were determined for each individual patient using spatially correlated SPECT and CT data sets, for each follow-up period. Average dose-effect relations for both subgroups were determined, as well as dose-effect relations for different regions. RESULTS: In general, partial improvement of local pulmonary injury was observed between 3 and 18 months for each of the three endpoints. After 18 months, no further improvement was seen. Patients with breast cancer and malignant lymphoma showed a similar improvement (except for the perfusion parameter), which was attributed to a recovery from the early radiation response and could not be explained by contraction effects of fibrosis of lung parenchyma. No regional differences in radiosensitivity 18 months after treatment were observed, except for the dorsal versus ventral region. This difference was attributed to a gravity-related effect in the measuring procedure. CONCLUSION: For all patients, a partial recovery from early local perfusion, ventilation, and density changes, was seen between 3 and 18 months after radiotherapy. After 18 months, local lung function did not further improve (lymphoma patients).

Adolescent↗
PubMed2000

Radiation dose-effect relations and local recovery in perfusion for patients with non-small-cell lung cancer.

PURPOSE: To determine local dose-effect relations for lung perfusion and density changes due to irradiation for patients with non-small-cell lung cancer (NSCLC) and to quantify the effect of reperfusion. METHODS AND MATERIALS: For 25 NSCLC patients and a reference group of 81 patients with healthy lungs, registered single photon emission computed tomography (SPECT) lung perfusion and CT scans were made, before and after radiotherapy. Average dose-effect relations for perfusion and CT-density changes were calculated and compared with the dose-effect relation of the reference group. On the basis of these dose-effect relations, the post-RT perfusion was predicted for each patient and compared to the measured post-RT perfusion. RESULTS: Well-perfused lung regions of the NSCLC patients showed the same dose-effect relation as the reference patients. By comparing predicted and measured post-treatment perfusion scans, regions of reperfusion could be determined for 18 of 25 NSCLC patients but for none of the reference patients. CONCLUSION: Well-perfused lung tissue of patients with NSCLC behaves like healthy lung tissue with respect to radiation. The dose-effect relation for perfusion and CT density was extended for doses up to 80 Gy. Radiation damage in poorly perfused lung regions was less than predicted as a consequence of local reperfusion.

Algorithms↗
PubMed1999

Effect of radiotherapy and chemotherapy on pulmonary function after treatment for breast cancer and lymphoma: A follow-up study.

PURPOSE: To determine the changes in pulmonary function tests (PFTs) 0 to 48 months after treatment for breast cancer and lymphoma. PATIENTS AND METHODS: The alveolar volume (V(A)), vital capacity, forced expiratory volume in 1 second, and corrected transfer factor of carbon monoxide (T(L,COc)) were measured in 69 breast cancer and 41 lymphoma patients before treatment and 3, 18, and 48 months after treatment with radiotherapy alone or radiotherapy in combination with chemotherapy (mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine; cyclophosphamide, epidoxorubicin, fluorouracil; cyclophosphamide, thiotepa, carboplatin; cyclophosphamide, methotrexate, fluorouracil). The three-dimensional dose distribution in the lung of each patient was converted to the mean lung dose. Statistical analysis was used to evaluate the changes in PFT values over time in relation to age, sex, smoking, chemotherapy, and the mean lung dose. RESULTS: After an initial reduction in PFT values at 3 months, significant recovery was seen at 18 months for all patients. Thereafter, no further improvement could be demonstrated. Reductions in spirometry values and V(A) were related to the mean lung dose only (0.9% per Gy at 3 months and 0.4% per Gy mean dose at 18 months). T(L,COc) decreased 1. 1% per Gy mean dose and additionally decreased 6% when chemotherapy was given after radiotherapy. Chemotherapy administered before radiotherapy reduced baseline T(L,COc) values by 8% to 21%. All patients showed an improvement of 5% at 18 months. CONCLUSION: On the basis of the mean lung dose and the chemotherapy regimen, the changes in PFT values can be estimated before treatment within 10% of the values actually observed in 72% to 85% of our patients with healthy lungs.

Adolescent↗
PubMed1998

Estimation of the incidence of late bladder and rectum complications after high-dose (70-78 GY) conformal radiotherapy for prostate cancer, using dose-volume histograms.

PURPOSE: To investigate whether Dose-Volume Histogram (DVH) parameters can be used to identify risk groups for developing late gastrointestinal (GI) and genitourinary (GU) complications after conformal radiotherapy for prostate cancer. METHODS AND MATERIALS: DVH parameters were analyzed for 130 patients with localized prostate cancer, treated with conformal radiotherapy in a dose-escalating protocol (70-78 Gy, 2 Gy per fraction). The incidence of late (>6 months) GI and GU complications was classified using the RTOG/EORTC and the SOMA/LENT scoring system. In addition, GI complications were divided in nonsevere and severe (requiring one or more laser treatments or blood transfusions) rectal bleeding. The median follow-up time was 24 months. We investigated whether rectal and bladder wall volumes, irradiated to various dose levels, correlated with the observed actuarial incidences of GI and GU complications, using volume as a continuous variable. Subsequently, for each dose level in the DVH, the rectal wall volumes were dichotomized using different volumes as cutoff levels. The impact of the total radiation dose, and the maximum radiation dose in the rectal and bladder wall was analyzed as well. RESULTS: The actuarial incidence at 2 years for GI complications > or =Grade II was 14% (RTOG/EORTC) or 20% (SOMA/LENT); for GU complications > or =Grade III 8% (RTOG/EORTC) or 21% (SOMA/LENT). Neither for GI complications > or =Grade II (RTOG/EORTC or SOMA/LENT), nor for GU complications > or =Grade III (RTOG/EORTC or SOMA/LENT), was a significant correlation found between any of the DVH parameters and the actuarial incidence of complications. For severe rectal bleeding (actuarial incidence at 2 years 3%), four consecutive volume cutoff levels were found, which significantly discriminated between high and low risk. A trend was observed that a total radiation dose > or = 74 Gy (or a maximum radiation dose in the rectal wall >75 Gy) resulted in a higher incidence of severe rectal bleeding (p = 0.07). CONCLUSIONS: These data show that dose escalation up to 78 Gy, using a conformal technique, is feasible. However, these data have also demonstrated that the incidence of severe late rectal bleeding is increased above certain dose-volume thresholds.

Dose-Response Relationship, Radiation↗
PubMed1998

Dose-effect relations for early local pulmonary injury after irradiation for malignant lymphoma and breast cancer.

PURPOSE: To quantify the influence of treatment- and patient-related factors on the severity of early local pulmonary injury and to establish whether regional differences are present for local dose-effect relations for early radiation-induced pulmonary injury. METHODS: Forty-two patients with malignant lymphoma and 40 breast cancer patients were examined prior to and 3 months after radiotherapy. The lymphoma patients were irradiated with mantle fields to an average dose of 38 Gy and the breast cancer patients were irradiated with internal mammary node fields with or without tangential breast fields to an average dose of 50 Gy. Dose-effect relations for local perfusion, ventilation and density changes were determined using correlated single photon emission computed tomography (SPECT) and CT data. A multivariate analysis was performed to study the influence of irradiated volume, chemotherapy (CMF and MOPP/ABV), smoking, age and gender. In addition, dose-effect relations for different regions in the lung were determined. RESULTS: A similar and almost linear increase of early functional changes as a function of radiation dose was observed for perfusion and ventilation, whereas the shape of the dose-effect relation and the magnitude of early structural changes were different for density. For the three end-points studied, regional differences in radiosensitivity could not be demonstrated. For the posterior lung region compared to the anterior lung region, however, a difference was observed, which could be attributed to a gravity-related effect in the measuring procedure. Local structural changes (density) were significantly smaller for smokers (P = 0.002) and young patients (P = 0.007), whereas the CMF chemotherapy regimen given after radiotherapy (P = 0.017) significantly increased the amount of functional changes (perfusion). The magnitude of local pulmonary changes was independent of the irradiated volume, the MOPP/ABV chemotherapy regimen and gender. CONCLUSION: The dose-effect relations for early radiation-induced local pulmonary changes were independent of the irradiated volume, MOPP/ABV, gender and lung region. CMF, smoking and age influenced the magnitude of early pulmonary changes and should be taken into account in dose-escalation protocols.

Adult↗
PubMed1998

Evaluation of two dose-volume histogram reduction models for the prediction of radiation pneumonitis.

PURPOSE: To evaluate the similarities between the mean lung dose and two dose-volume histogram (DVH) reduction techniques of 3D dose distributions of the lung. PATIENTS AND METHODS: DVHs of the lungs were calculated from 3D dose distributions of patients treated for malignant lymphoma (44), breast cancer (42) and lung cancer (20). With a DVH reduction technique, a DVH is summarized by the equivalent uniform dose (EUD), a quantity which is directly related to the normal tissue complication probability (NTCP). Two DVH reduction techniques were used. The first was based on an empirical model proposed by Kutcher et al. (Kutcher, G.J., Burman, C., Brewster, M.S., Goitein, M. and Mohan, R. Histogram reduction method for calculating complication probabilities for three-dimensional treatment planning evaluations. Int. J. Radiat. Oncol. Biol. Phys. 21: 137-146, 1991), which needs a volume exponent n. Several values for n were tested. The second technique was based on a radiobiological model, the parallel functional subunit model developed by Niemierko et al. (Niemierko, A. and Goitein, M. Modeling of normal tissue response to radiation: the critical volume model. Int. J. Radiat. Oncol. Biol. Phys. 25: 135-145, 1993) and Jackson et al. (Jackson, A., Kutcher, G.J. and Yorke, E.D. Probability of radiation-induced complications for normal tissues with parallel architecture subject to non-uniform irradiation. Med. Phys. 20: 613-625, 1993), for which a local dose-effect relation needed to be specified. This relation was obtained from an analysis of perfusion and ventilation SPECT data. RESULTS: It can be shown analytically that the two DVH reduction techniques are identical, if the local dose-effect relation obeys a power-law relationship in the clinical dose range. Local dose-effect relations based on perfusion and ventilation SPECT data can indeed be fitted with a power-law relationship in the range 0-80 Gy, from which values of n = 0.8-0.9 were deduced. These correspond to the commonly used value of n = 0.87 for lung tissue and yielded EUDn=0.87 values which were almost identical to the mean lung doses. For other n values, for which no experimental data are present, differences exist between EUD and mean dose values. Six patients with malignant lymphoma (6/44) and none of the breast cancer patients (0/42) developed radiation pneumonitis. These cases occurred only at high values for the mean lung dose. CONCLUSION: The two DVH reduction techniques are identical for lung and are very similar to mean dose calculations. The two techniques are also relatively similar for other model parameter values.

Breast Neoplasms↗
PubMed1998

Prediction of overall pulmonary function loss in relation to the 3-D dose distribution for patients with breast cancer and malignant lymphoma.

PURPOSE: To predict the changes in pulmonary function tests (PFTs) 3-4 months after radiotherapy based on the three-dimensional (3-D) dose distribution and taking into account patient- and treatment-related factors. METHODS: For 81 patients with malignant lymphoma and breast cancer, PFTs (VA, VC, FEV1 and TL,COc) were performed prior to and 3-4 months after irradiation and dose-effect relations for early changes in local perfusion, ventilation and air-filled fraction were determined using correlated CT and SPECT data. The 3-D dose distribution of each patient was converted into four different dose-volume parameters, i.e. the mean dose in the lung and three overall response parameters (ORPs, which represent the average local injury over the complete lung). ORPs were determined using the dose-effect relations for early changes in local perfusion, ventilation and air-filled fraction. Correlation coefficients were calculated between these dose-volume parameters and the changes in PFTs. In addition, the impact of the variables chemotherapy (MOPP/ABV and CMF), tamoxifen, smoking, age and gender on the relation between the mean lung dose and the relative changes in PFTs following radiotherapy was studied using multiple regression analysis. RESULTS: The mean lung dose proved to be the easiest parameter to predict the reduction in PFTs 3-4 months following radiotherapy. For all patients the relation between the mean lung dose and the changes in PFTs could be described with one regression line through the origin and a slope of 1% reduction in PFT for each increase of 1 Gy in mean lung dose. Smoking and CMF chemotherapy influenced the reduction in PFTs significantly for VA and TL,COc, respectively. Patients treated with MOPP/ABV prior to radiotherapy had lower pre-radiotherapy PFTs than other patient groups, but did not show further deterioration after radiotherapy (at 3-4 months). CONCLUSIONS: The relative reduction in VA, VC, FEV1 and TL,COc 3-4 months after radiotherapy for breast cancer and malignant lymphoma can be estimated before radiotherapy based on the mean lung dose of each individual patient and taking into account the use of chemotherapy and smoking habits of the patient.

Adolescent↗
PubMed1998

Automatic three-dimensional matching of CT-SPECT and CT-CT to localize lung damage after radiotherapy.

UNLABELLED: The aim of this study was to develop a fast and clinically robust automatic method to register SPECT and CT scans of the lungs. METHODS: CT and SPECT scans were acquired in the supine position from 20 patients with healthy lungs. After partial irradiation of the lungs by radiotherapy, the scans were repeated. Two matching methods were compared: a conventional method with external skin markers and a new method using chamfer matching of the lung contours. In the latter method, a unique value for the SPECT threshold, needed for segmentation of the SPECT lungs, was determined by iteratively applying the chamfer matching algorithm. RESULTS: The new technique for CT-SPECT matching could be implemented in a fully automatic manner and required less than 2 min. No large systematic shifts or rotations were present between the matches obtained with the marker method and the lung contour method for healthy or partially irradiated lungs. For healthy lungs, the number of ventilation SPECT counts outside the CT-defined lung was taken as a measure for a good match. This number of outside counts was slightly lower for the new method than for the conventional method, which indicates that the accuracy of the new method is at least comparable to the conventional method. For ventilation, a systematic difference between the results of the matching methods, a small translation in the anterior --> posterior direction, could be attributed to an inconsistency of the marker positions (2 mm). For perfusion, a somewhat larger anterior --> posterior shift was found, which was attributed to the gravity force. CT-CT correlation on the lung contours using chamfer matching was tested with the same dataset. For accurate matching, the CT slices encompassing the diaphragm had to be deleted. CONCLUSION: The new method based on lung contour matching is a fast, automatic procedure and allows accurate clinical follow-up.

Humans↗
PubMed1996

Recovery of overall and local lung function loss 18 months after irradiation for malignant lymphoma.

PURPOSE: To determine the local and overall pulmonary injury 3 to 18 months after irradiation and to investigate whether the changes in overall lung function can be predicted using the three-dimensional (3-D) dose distribution in combination with dose-effect relations for local injury; and to study the influence of chemotherapy on the injury. PATIENTS AND METHODS: Local perfusion (Q), ventilation (V), and tissue density were measured in 25 patients treated for malignant lymphoma, before, 3 to 4 months after, and 18 months after irradiation. Dose-effect relations for local injury, calculated using correlated single-photon emission computed tomographic (SPECT) and computed tomographic (CT) data, were combined with the 3-D dose distribution, to calculate the estimated mean local changes over the complete lung for each patient. The result was correlated with the actual changes in pulmonary function. RESULTS: A dose-dependent increase with injury was observed at 3 to 4 months after irradiation, which at 18 months had recovered by approximately 50% to 60%. The estimated mean relative reduction of local Q predicted the change in overall lung function within 10% of the actually observed values in 63% to 73% of patients. Chemotherapy given before radiotherapy enhanced radiation-induced reduction of local Q significantly, with dose-modifying factors of 1.22 and 1.37 at 3 to 4 months and 18 months, respectively. CONCLUSION: Partial recovery of radiation-induced reduction of local and overall lung function was observed at 18 months after irradiation. The overall functional outcome of most patients could be well predicted, based on the estimated mean local injury over the complete lung. Chemotherapy given before radiotherapy enhanced the radiation-induced reduction of local Q.

Adolescent↗
PubMed1996

Radiation pneumonitis imaged with indium-111-pentetreotide.

UNLABELLED: Early recognition of radiation pneumonitis enables adequate treatment with a reasonable chance to prevent late sequelae. The feasibility of 111In-pentetreotide in detecting this condition was explored in this study. METHODS: The degree of lung uptake of 111In-pentetreotide, evaluated both visually and quantitatively by irradiated-to-nonirradiated area ratios (INIA ratio) from planar images after 24 hr, was analyzed in relation to the radiation field and compared with ventilation/perfusion (V/Q) images and chest radiographs or CT in 11 patients who had received radiotherapy to the mediastinum or to the internal mammary nodes, 10 of whom were suspected of having clinical radiation pneumonitis. Additional SPECT studies were used to map lung uptake distribution. RESULTS: Indium-111-pentetreotide scans were positive in nine symptomatic patients examined 2-5 mo after radiotherapy; strongly or moderately positive in eight patients, one of whom was receiving steroid therapy without clinical response; and weakly positive in one patient with good steroid response. Indium-111-pentetreotide studies were negative in one asymptomatic patient examined 1 mo after radiotherapy and in one symptomatic patient, with subsequent diagnosis of aspecific viral pneumonitis, examined 4 mo after irradiation. Positive 111In-pentetreotide scans delineated areas of radiation pneumonitis that adequately correlated with areas of decreased ventilation/perfusion and x-ray abnormalities. INIA ratios varied from 1.01 to 2.16 and, in irradiated areas with visible uptake, the lowest value was 1.29. SPECT showed lung uptake in both superficial and deep lying areas in patients with mantle irradiation fields whereas distribution was limited to anterior areas in internal mammary lymph node chain irradiation. CONCLUSION: Indium-111-pentetreotide can detect radiation pneumonitis and may have a role in both the differential diagnosis of patients who have complaints after radiotherapy, and when supported by quantification in the monitoring of response to steroid therapy.

Feasibility Studies↗
PubMed1995

Estimation of overall pulmonary function after irradiation using dose-effect relations for local functional injury.

PURPOSE: To predict the pulmonary function 3-4 months after irradiation for malignant lymphoma from the three-dimensional (3-D) dose distribution. METHODS: Dose-effect relations for the relative reduction of local perfusion (Q) and local ventilation (V), were calculated in 25 patients, using correlated SPECT (Single Photon Emission Computed Tomography) and CT data. By combining the 3-D dose distribution of an individual patient with the dose-effect relations averaged over all patients, the average reduction of local Q and V (i.e., the overall response parameters) in the whole lung was estimated for each patient. Correlation coefficients were calculated between these overall response parameters and the change in standard lung function tests. In addition, the relation between the overall response parameters and the incidence of radiation pneumonitis was determined. RESULTS: The overall response parameter for perfusion was correlated with the change in standard lung function tests, with correlation coefficients varying between 0.53 (p = 0.007) and 0.71 (p < 0.001) for the change of Vital Capacity and Forced Expiratory Volume at 1 s, respectively. For the overall response parameter for ventilation similar correlations were observed. Four out of the 25 patients developed radiation pneumonitis; in these four patients the overall response parameter for perfusion was on average somewhat higher (13.2 +/- 1.4% (1 standard error of the mean)) than in patients without radiation pneumonitis (10.5 +/- 1.0%), but this difference was not significant. A higher incidence of radiation pneumonitis was observed for larger values of the overall response parameter for perfusion; in patient groups with an overall response parameter for perfusion of 0-5%, 5-10%, 10-15%, and 15-20%, the incidence of radiation pneumonitis was 0 (0/1), 10 (1/10), 13 (1/8) and 33% (2/6), respectively. CONCLUSION: By combining the 3-D dose distribution with the average dose-effect relations for local perfusion or ventilation, an overall response parameter can be calculated prior to irradiation, which is predictive for the radiation-induced change in the overall pulmonary function, and possibly for the incidence of radiation pneumonitis, in this group of patients.

Adolescent↗
PubMed1994

Dose-effect relations for local functional and structural changes of the lung after irradiation for malignant lymphoma.

PURPOSE: To estimate the dose-effect relations for local functional (ventilation and perfusion) and structural (density) changes of the lung, 3-4 months after irradiation. METHODS: Twenty-five patients with malignant lymphoma were irradiated with a (modified) mantle field to an average dose of 38 Gy, given in 21 fractions. Single photon emission computed tomography (SPECT) ventilation (V) and perfusion (Q) scans, and CT scans were performed before and 3-4 months after radiation treatment. The three-dimensional dose distribution was calculated using the CT data. After correlation of SPECT and CT data sets, the average post-treatment value of V, Q and lung density per voxel was calculated relative to the pre-treatment value, per dose interval of 4 Gy. Subsequently, the dose-effect relations in each patient were normalized to the average value per voxel in the dose interval of 0-12 Gy. In addition, in each dose interval of 4 Gy the fraction of patients with changes larger than 20% was calculated for all three parameters. The dose-effect relations for perfusion and ventilation normalized to the low-dose regions, and the dose-incidence curves for the fraction of patients with changes larger than 20% were fitted for all three parameters, using a logistic model. RESULTS: Marked changes in the distribution of V and Q were found after irradiation. Prior to normalization to the low-dose regions, a change in V and Q was found in most patients in the dose interval of 0-12 Gy, varying from an increase of 37% to a decrease of 10%, which was followed by a decreasing trend at higher doses. The increase in the low-dose regions indicated a redistribution phenomenon, the magnitude of which was dependent of the irradiated volume. The logistic fit of the dose-effect relations for Q and V, normalized to the low-dose regions, resulted in values for D50 of 51 Gy and 54 Gy (given in 21 fractions on average), respectively, and for the steepness parameter k of 4.2 and 4.0, respectively. The logistic fit for the dose-incidence curves for Q, V and lung density resulted in values for D50 and k of 38 Gy, 37 Gy, 44 Gy and 10.3, 7.8 and 9.4, respectively. CONCLUSIONS: With the combined use of SPECT and CT scans, we have obtained dose-effect relations for local functional and structural damage in the lung, 3-4 months after irradiation.

Adolescent↗
PubMed1994

Quantifying local lung perfusion and ventilation using correlated SPECT and CT data.

UNLABELLED: A clinically applicable method for quantifying lung perfusion and ventilation on a subregional (local) scale from SPECT scans in order to estimate local lung function in patients with pre-existing pulmonary disease and to monitor local treatment effects was developed and evaluated. METHODS: SPECT 99mTc perfusion and 81mKr ventilation images were corrected for photon attenuation and scatter effect with a postreconstruction correction method incorporating a variable-effective linear-attenuation coefficient calculated from spatially-correlated CT data. A new algorithm was developed to quantify local ventilation from the SPECT data, which, in contrast with other algorithms, makes no assumptions on ventilation homogeneity over the lung. The quantification procedure was applied to clinical data from patients with a normal lung function and from patients suffering from radiation-induced pulmonary dysfunction. RESULTS: The calculated attenuation correction factors on the observed number of counts in the lung range from 2.0 to 3.0 and 2.3 to 3.5 for 81mKr and 99mTc, respectively, showing a systematic increase from the diaphragm to the lung apex. As a result of this correction, the values of local perfusion and ventilation differ 10%-15% from values calculated without attenuation correction. The calculated values of the local ventilation are 10%-50% lower than those found by quantification algorithms which assume homogeneous ventilation. CONCLUSIONS: The methods presented here are robust with respect to uncertainties in the input parameters and yield realistic values for perfusion and ventilation distribution in the lung with an intrinsic accuracy (largely determined by count statistics) of about 10%.

Algorithms↗
PubMed1993

A new method to determine dose-effect relations for local lung-function changes using correlated SPECT and CT data.

PURPOSE: To determine dose-effect relations for regional lung-function changes after radiotherapy. METHODS: Single Photon Emission Computed Tomography (SPECT) was performed to quantify regional ventilation and perfusion. CT scans were used to calculate the three-dimensional (3-D) dose distribution. Both SPECT and CT scans were performed prior to radiotherapy and 5 months after the start of the treatment. To obtain combined 3-D information on ventilation, perfusion and dose, the SPECT data were correlated with the corresponding CT data. The relative changes in ventilation and perfusion were calculated in each SPECT voxel (voxel size about 6 x 6 x 6 mm) and related to the dose in that voxel. The average relative changes were determined per dose interval of 4 Gy. This procedure was evaluated using the data from five patients treated for Hodgkin's disease with mantle field irradiation with a prescribed total dose of 40-42 Gy. RESULTS: Dose-effect relations for perfusion were observed in all patients, while in four of the five patients, a dose-effect relation was found for ventilation. The maximal uncertainty of the calculated radiation dose was 11%: a difference between the position of the patient during treatment and during CT scanning caused a maximal dose uncertainty of 6%, while the accuracy of the dose calculation algorithm itself was estimated to be within 5%. CONCLUSION: The results indicate that the combined use of SPECT and CT information is an effective method for determining dose-effect relations for regional lung function parameters in each individual patient.

Adolescent↗