Pre- and postoperative 68 Ga-DOTATOC positron emission tomography for hormone-secreting pituitary neuroendocrine tumours.

OBJECTIVES: Somatostatin receptors (SSTRs) are potential targets for detecting pituitary neuroendocrine tumours (PitNETs) that can be visualized effectively with 68 Ga-labelled PET tracers. With this study, we have evaluated the diagnostic properties of such a tracer, 68 Ga-DOTATOC, in patients with hormone-producing PitNETs before and after surgery. DESIGN/METHODS: This prospective case-control study presents preoperative positron emission tomography (PET) and histopathological data in 18 patients with somatotroph (n = 8), corticotroph (n = 7) and thyrotroph (n = 3) PitNETs. Patients were scanned pre- and postoperatively with 68 Ga-DOTATOC PET. For the postoperative part of the study, patients with gonadotroph tumours (n = 7) were also included. Fifteen pituitary healthy controls underwent the same protocol once. The maximum standard uptake value (SUVmax ) was analysed in manually outlined regions around the tumour in patients and around the pituitary gland in controls. specimens were collected during surgery in subjects for assessment of adenohypophyseal tumour cell type and the SSTR expression. RESULTS: Thyrotroph tumours showed higher uptake (median SUVmax 41.1; IQR 37.4-60.0) and corticotroph tumours lower uptake (SUVmax 6.8; 2.6-9.3) than normal pituitary gland (SUVmax 13.8; 12.1-15.5). The uptake in somatotroph tumours (SUVmax 15.9; 11.6-19.7) was similar to the uptake in the pituitary gland. There was a strong correlation between SUVmax and SSTR2 expression (r = .75 (P < .01)). In the postoperative evaluation, PET was able to correlate tracer uptake with biochemical cure and noncure in patients with an abnormal postoperative magnetic resonance image and a preoperative tumour uptake SUVmax  > 13.8. CONCLUSIONS: 68 Ga-DOTATOC PET can be used to detect thyrotroph tumours in the pre- and postoperative imaging assessment. Corticotroph tumours had a significantly lower uptake compared to the pituitary gland but without a distinct increased tumour uptake the clinical postoperative value is limited.

Lower 68 Ga-DOTATOC uptake in nonfunctioning pituitary neuroendocrine tumours compared to normal pituitary gland-A proof-of-concept study.

OBJECTIVES: 68  Ga-DOTATOC PET targets somatostatin receptors (SSTRs) and is well established for the detection of SSTR-expressing tumors, such as gastrointestinal neuroendocrine tumors. Pituitary adenomas, recently designated as pituitary neuroendocrine tumors (PitNETs), also express SSTRs, but there has been no previous evaluations of 68  Ga-DOTATOC PET in PitNET patients. The aim of this pilot study was to evaluate the diagnostic properties of 68  Ga-DOTATOC PET in the most common PitNET, ie non-functioning (NF)-PitNET. DESIGN/PATIENTS: NF-PitNET patients (n = 9) and controls (n = 13) were examined preoperatively with 68  Ga-DOTATOC PET for 45 min after tracer injection in dynamic list mode. Tumor specimens were collected during surgery in patients. MRI and PET images were co-registered using PMOD software. The maximum standard uptake value (SUVmax ) was analyzed in manually outlined regions of interest (ROI) around the tumor in patients and around the pituitary gland in controls. Immunohistochemical analyses were conducted on tumor specimens for assessment of tumor cell type and SSTR expression. RESULTS: Median SUVmax (IQR) was lower in patients than in controls (3.9 [3.4-8.5] vs 14.1 [12.5-15.9]; P < .01]. In ROC analysis, the area under the curve was 0.87 (P < .01) for SUVmax , with 78% sensitivity and 92% specificity. Immunohistochemical analysis showed NF-PitNETs were of gonadotroph (n = 7) and corticotroph (n = 2) origin. SSTR expression was high for SSTR3, low-to-moderate for SSTR2, and low for SSTR1 and SSTR5. CONCLUSIONS: This proof-of-concept study shows that 68 Ga-DOTATOC PET can be used to differentiate between normal pituitary tissue and NF-PitNET.

Improvements of 177Lu SPECT images from sparsely acquired projections by reconstruction with deep-learning-generated synthetic projections.

BACKGROUND: For dosimetry, the demand for whole-body SPECT/CT imaging, which require long acquisition durations with dual-head Anger cameras, is increasing. Here we evaluated sparsely acquired projections and assessed whether the addition of deep-learning-generated synthetic intermediate projections (SIPs) could improve the image quality while preserving dosimetric accuracy. METHODS: This study included 16 patients treated with 177Lu-DOTATATE with SPECT/CT imaging (120 projections, 120P) at four time points. Deep neural networks (CUSIPs) were designed and trained to compile 90 SIPs from 30 acquired projections (30P). The 120P, 30P, and three different CUSIP sets (30P + 90 SIPs) were reconstructed using Monte Carlo-based OSEM reconstruction (yielding 120P_rec, 30P_rec, and CUSIP_recs). The noise levels were visually compared. Quantitative measures of normalised root mean square error, normalised mean absolute error, peak signal-to-noise ratio, and structural similarity were evaluated, and kidney and bone marrow absorbed doses were estimated for each reconstruction set. RESULTS: The use of SIPs visually improved noise levels. All quantitative measures demonstrated high similarity between CUSIP sets and 120P. Linear regression showed nearly perfect concordance of the kidney and bone marrow absorbed doses for all reconstruction sets, compared to the doses of 120P_rec (R2 ≥ 0.97). Compared to 120P_rec, the mean relative difference in kidney absorbed dose, for all reconstruction sets, was within 3%. For bone marrow absorbed doses, there was a higher dissipation in relative differences, and CUSIP_recs outperformed 30P_rec in mean relative difference (within 4% compared to 9%). Kidney and bone marrow absorbed doses for 30P_rec were statistically significantly different from those of 120_rec, as opposed to the absorbed doses of the best performing CUSIP_rec, where no statistically significant difference was found. CONCLUSION: When performing SPECT/CT reconstruction, the use of SIPs can substantially reduce acquisition durations in SPECT/CT imaging, enabling acquisition of multiple fields of view of high image quality with satisfactory dosimetric accuracy.

Routine preoperative (111)In-octreotide scintigraphy in patients with medullary thyroid cancer.

BACKGROUND: Surgery is the only potential cure for patients with medullary thyroid carcinoma (MTC). Preoperative ultrasound, computed tomography and magnetic resonance imaging are not sensitive enough for detection of microscopic disease. The aim of this study was to investigate if routine preoperative (111)In-labelled (DTPA-D-Phe(1))-octreotide scintigraphy (SRS) could be used as a staging procedure in planning primary surgery in patients with MTC. METHODS: This study included patients with primary sporadic clinically overt MTC diagnosed between 1996 and 2009. All patients underwent conventional imaging of neck and thorax and SRS prior to standardised surgery. The findings on SRS were correlated to the findings on conventional imaging, histopathology and to postoperative biochemical results and survival. RESULTS: A total of 19 patients with sporadic MTC were enrolled. Median follow-up was 77(9-184) months. SRS visualised the primary tumour in 16 (84 %) patients. Fifteen (79 %) patients had locoregional lymph node metastases, but SRS detected metastatic lesions in only 8 (53 %) patients. In three patients with distant spread, SRS failed to detect metastatic lesions in two. At latest follow-up, six (32 %) patients had died, nine (47 %) patients were alive with elevated tumour markers, and four (21 %) patients were considered in complete biochemical remission. CONCLUSIONS: This study provided further evidence that SRS, compared to conventional imaging, is fairly sensitive for detection of primary MTC but not metastatic disease. Although preoperative SRS may be of prognostic value, there is no indication for its routine use as a staging procedure in planning primary surgery.

Evaluation of reconstruction methods and image noise levels concerning visual assessment of simulated liver lesions in 111In-octreotide SPECT imaging.

BACKGROUND: Early cancer detection is crucial for patients' survival. The image quality in 111In-octreotide SPECT imaging could be improved by using Monte Carlo (MC)-based reconstruction. The aim of this observational study was to determine the detection rate of simulated liver lesions for MC-based ordered subset expectation maximization (OSEM) reconstruction compared to conventional attenuation-corrected OSEM reconstruction. METHODS: Thirty-seven SPECT/CT examinations with 111In-octreotide were randomly selected. The inclusion criterion was no liver lesions at the time of examination and for the following 3 years. SPECT images of spheres representing lesions were simulated using MC. The raw data of the spheres were added to the raw data of the established healthy patients in 26 of the examinations, and the remaining 11 examinations were not modified. The images were reconstructed using conventional OSEM reconstruction with attenuation correction and post filtering (fAC OSEM) and MC-based OSEM reconstruction without and with post filtering (MC OSEM and fMC OSEM, respectively). The images were visually and blindly evaluated by a nuclear medicine specialist. The criteria evaluated were liver lesion yes or no, including coordinates if yes, with confidence level 1-3. The percentage of detected lesions and accuracy (percentage of correctly classified cases), as well as tumor-to-normal tissue concentration (TNC) ratios and signal-to-noise ratios (SNRs), were evaluated. RESULTS: The detection rates were 30.8% for fAC OSEM, 42.3% for fMC OSEM, and 50.0% for MC OSEM. The accuracies were 45.9% for fAC OSEM, 45.9% for fMC OSEM, and 54.1% for MC OSEM. The number of false positives was higher for fMC and MC OSEM. The observer's confidence level was higher in filtered images than in unfiltered images. TNC ratios were significantly higher, statistically, with MC OSEM and fMC OSEM than with AC OSEM, but SNRs were similar due to higher noise with MC OSEM. CONCLUSION: One in two lesions were found using MC OSEM versus one in three using conventional reconstruction. TNC ratios were significantly improved, statistically, using MC-based reconstruction, but the noise levels increased and consequently the confidence level of the observer decreased. For further improvements, image noise needs to be suppressed.

Radiation exposure during liver surgery after treatment with (90)Y microspheres, evaluated with computer simulations and dosimeter measurements.

PURPOSE: Two patients with liver tumours were planned for a combined treatment, including surgery with preceding injections of ß(-) radiation emitting (90)Y microspheres (SIRTEX(®)). The aim of this paper is to present a method of pre-surgical computer simulations of the absorbed dose rate on the surface of tumour tissue, combined with measurements of the actual absorbed dose rate on resected tissue, in order to estimate the absorbed dose to a surgeon's fingers during such surgery procedures. METHODS AND MATERIALS: The dose rates from ß(-) radiation on the surface of tumour tissue were simulated with the software VARSKIN(®) Mod 2. The activity concentrations in tumours were estimated, based on SPECT/CT distribution studies of (99m)Tc-MAA and confirmed by SPECT/CT bremsstrahlung studies of (90)Y microspheres. The activity distributions were considered as homogeneous within the tumour regions. The absorbed dose rates at different tumour tissue spots were calculated based on measurements with thermo-luminescent dosimeters (TLD) fastened on resected tissue. RESULTS: The simulations showed a good agreement with the averaged absorbed dose rates based on TLD measurements performed on resected tissue, differing by 13% and 4% respectively. The absorbed dose rates at the measured maximum hotspots were twice as high as the average dose rates for both patients. CONCLUSION: The data is not sufficient in order to draw any general conclusions about dose rates on tumour tissue during similar surgeries, neither about the influence of dose rate heterogeneities nor about average dose rates. However, the agreement between simulations and measurements on these limited data indicate that this approach is a promising method for estimations of the radiation exposure to the surgeons' fingers during this kind of surgery procedure. More data from similar surgeries are necessary in order to validate the method.

EVALUATION OF THE SPATIAL RESOLUTION IN MONTE CARLO-BASED SPECT/CT RECONSTRUCTION OF 111IN-OCTREOTIDE IMAGES.

The purpose was to evaluate the spatial resolution in 111In-octreotide single-photom emission computed tomography (SPECT)/computed tomography (CT) imaging following reconstructions with three different ordered subset expectation maximizations (OSEM) reconstruction algorithms; attenuation corrected (AC) OSEM, AC OSEM with resolution recovery (ACRR OSEM) and Monte Carlo-based OSEM reconstruction (MC OSEM). SPECT/CT imaging of a triple line phantom containing 111In in air and water was performed. The spatial resolution, represented by the full width at half maximum (FWHM) of a line profile, was determined for each line, for X and Y direction and for all reconstructions. The mean FWHM was 12.2 mm (±standard deviation [SD] 3.7 mm) for AC OSEM, 9.3 mm (±SD 2.5 mm) for ACRR OSEM and 8.2 mm (±SD 2.0 mm) for MC OSEM. MC-based SPECT/CT reconstruction clearly improves the spatial resolution in 111In-octreotide imaging and since MC simulations can be performed for all photon energies MC OSEM has the potential to improve SPECT/CT imaging overall.

Bone Marrow Absorbed Doses and Correlations with Hematologic Response During 177Lu-DOTATATE Treatments Are Influenced by Image-Based Dosimetry Method and Presence of Skeletal Metastases.

This study aimed to compare different image-based methods for bone marrow dosimetry and study the dose-response relationship during treatment with 177Lu-DOTATATE in patients with and without skeletal metastases. Methods: This study included 46 patients with advanced neuroendocrine tumors treated with at least 2 fractions of 177Lu-DOTATATE at Sahlgrenska University Hospital. High- and low-uptake compartments were automatically outlined in planar images collected at 2, 24, 48, and 168 h after injection. The bone marrow absorbed doses were calculated from the cross doses of the high- and low-uptake compartments and the self-dose, using the time-activity concentration curve for the low-uptake compartment. This time-activity concentration curve was adjusted using a fixed constant of 1.8 for the planar dosimetry method and using the activity concentrations in vertebral bodies in SPECT images at 24 h after injection of 177Lu-DOTATATE in 4 hybrid methods: L4-SPECT used the activity concentration in the L4 vertebra, whereas V-SPECT, L-SPECT, and T-SPECT used the median activity concentration in all visible vertebrae, lumbar vertebrae, and thoracic vertebrae, respectively. Results: Using the planar method, L4-SPECT, V-SPECT, L-SPECT, and T-SPECT, the estimated median bone marrow absorbed doses were 0.19, 0.36, 0.40, 0.39, and 0.46 Gy/7.4 GBq, respectively, with respective ranges of 0.12-0.33, 0.15-1.44, 0.19-1.71, 0.21-1.60, and 0.18-2.12 Gy/7.4 GBq. For all methods, the bone marrow absorbed dose significantly correlated with decreased platelet counts. This correlation increased after treatment fraction 2: the Spearman correlation (rs) were -0.49 for the planar method, -0.61 for L4-SPECT, -0.63 for V-SPECT, -0.63 for L-SPECT, and -0.57 for T-SPECT. A separate analysis revealed an increased correlation for patients without skeletal metastases using the planar method (rs = -0.67). In contrast, hybrid methods had poor correlations for patients without metastases and stronger correlations for patients with skeletal metastases (rs = -0.61 to -0.74). The mean bone marrow absorbed doses were 3%-69% higher for patients with skeletal metastases than for patients without. Conclusion: The estimated bone marrow absorbed doses by image-based techniques and the correlation with platelets are influenced by the choice of measured vertebrae and the presence of skeletal metastases.

Normal limits for left ventricular ejection fraction and volumes determined by gated single photon emission computed tomography--a comparison between two quantification methods.

To compare gender-related normal limits for left ventricular (LV) ejection fraction (EF), end-diastolic and end-systolic volumes (EDV and ESV), obtained using two myocardial perfusion-gated single photon emission computed tomography (SPECT) quantification methods. A total of 185 patients were retrospectively selected from a consecutive series of patients examined for coronary artery disease (CAD) or for management of known CAD. Patients were included in the study group if they had normal or probably normal results with stress and rest perfusion imaging and if the combined interpretation of perfusion studies and gated rest studies showed no signs or suspicion of myocardial infarction. The gated SPECT studies were performed using a 2-day stress/gated rest Tc-99m sestamibi protocol. All patient studies were processed using CAFU and quantitative-gated SPECT (QGS), the two software packages for quantification of gated SPECT images. The lower normal limits for EF were higher for CAFU compared with QGS for both women (59% versus 53%) and men (54% versus 47%). The upper normal limits for EDV were also higher for CAFU compared with QGS for both women (133 versus 107 ml) and men (182 versus 161 ml). The differences between the software packages were small for ESV (women 44 versus 44 ml; men 69 versus 74 ml). Gender-specific normal limits need to be applied for LV EF and volumes determined by gated SPECT. Separate criteria for abnormal LV EF and EDV need to be used for women and men depending on the software package used.

Can nuclear medicine technologists assess whether a myocardial perfusion rest study is required?

UNLABELLED: Both stress and rest imaging are usually performed to diagnose ischemia or infarction in the left ventricle. If the stress study is performed first and the images indicate normal findings, it might be unnecessary to perform the rest study. The current study determines whether nuclear medicine technologists can assess the necessity of a rest study. METHODS: The results of gated SPECT performed using a 2-d nongated stress and gated rest (99m)Tc-sestamibi protocol for 532 consecutive patients were studied. Myocardial perfusion imaging was performed for diagnosing coronary artery disease (CAD) in 421 patients and for managing known CAD in 107 patients; 4 patients were examined for other reasons. Seventy-nine patients had previous myocardial infarction. Visual interpretation by 1 experienced physician at the time of clinical reporting was used as the gold standard for determining the scintigraphic presence of myocardial infarction or ischemia; rest, stress, and gated rest images and clinical information were available to this physician. All cases categorized as infarction or ischemia present or probably present were categorized as the group requiring a rest study (i.e., the "rest-study-required group"), whereas all other cases were categorized as the group not requiring a rest study (i.e., the "no-rest-study-required group"). A total of 3 physicians and 3 technologists independently interpreted the nongated stress images (slice images and polar plots) and decided whether a rest study was required. RESULTS: In the rest-study-required group, the 3 technologists correctly classified on average 171 of the 172 cases, and the 3 physicians correctly classified 169 (a difference that was not statistically significant). In the no-rest-study-required group, the physicians correctly classified 32% and the technologists 21% of the cases (P = 0.001). The risk that a patient sent home without a rest study would have been diagnosed with infarction or ischemia using the combined stress-rest interpretation was 1.3% (1/75) for the technologists and 2.6% (3/115) for the physicians. CONCLUSION: The nuclear medicine technologists were able to assess whether a rest study was needed; the risk that this assessment would be incorrect was not higher for the technologists than it was for the physicians. This type of assessment by a nuclear medicine technologist could be of value in efforts to improve effectiveness at a nuclear medicine clinic.

Autoradiography and biopsy measurements of a resected hepatocellular carcinoma treated with 90 yttrium radioembolization demonstrate large absorbed dose heterogeneities.

PURPOSE: Radioembolization is an alternative palliative treatment for hepatocellular carcinoma. Here, we examine the uptake differences between tumor tissue phenotypes and present a cross-section of the absorbed dose throughout a liver tissue specimen. METHODS AND MATERIALS: A patient with hepatocellular carcinoma was treated with 90Y radioembolization followed by liver tissue resection. Gamma camera images and autoradiographs were collected and biopsy tissue samples were analyzed using a gamma well counter and light microscopy. RESULTS: An analysis of 25 punched biopsy tissue samples identified 4 tissue regions: Normal tissue, viable tumor tissue with and without infarcted areas, and tumor areas with postnecrotic scar tissue. Autoradiography and biopsy tissue sample measurements showed large dose differences between viable and postnecrotic tumor tissue (159 Gy vs 23 Gy). CONCLUSIONS: Radioembolization of 90 yttrium with resin microspheres produces heterogeneous-absorbed dose distributions in the treatment of unifocal hepatic malignancies that could not be accurately determined with current gamma camera imaging techniques.

A comparison of two imaging modalities for detecting lymphatic nodal spread in radiochemotherapy of locally advanced cervical cancer.

BACKGROUND AND PURPOSE: In uterine cervical cancer tumour spread reaching the para-aortic lymph nodes is the most significant independent pre-treatment predictor of progression-free survival. When introducing [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET)/computed tomography (CT) in our clinic for patients with advanced cervical cancer planned for definitive radiochemotherapy, the purpose of this study was to quantify to what extent the added information lead to changes in radiotherapy planning. MATERIAL AND METHODS: We included 25 consecutive patients with cervical cancer stages IB2 - IIIB planned for definitive radiochemotherapy between November 2010 and May 2012. The patients were examined both with magnetic resonance imaging (MRI) and FDG-PET/CT before treatment and after four weeks of treatment. RESULTS: In 11/24 (46%) of the patients the FDG-PET/CT before treatment provided additional diagnostic information leading to changes in treatment planning compared to information from MRI. Seven of these eleven patients (64%) were alive and without evidence of disease at four-year follow-up. The MRI detected pelvic tumour spread not seen on the FDG-PET/CT in 2/24 patients. The disease-free four-year survival was 59%. CONCLUSIONS: Additional diagnostic information from FDG-PET/CT changed treatment strategy in almost half of the patients and may have increased chances of survival in this limited group of patients with locally advanced uterine cervical cancer. We recommend both modalities for nodal detection.

Segmentation of Whole-Body Images into Two Compartments in Model for Bone Marrow Dosimetry Increases the Correlation with Hematological Response in 177Lu-DOTATATE Treatments.

BACKGROUND: In 177Lu-DOTATATE treatments, bone marrow (BM) is one of the most important organs at risk. The authors previously developed an image-based two-compartment method for BM dosimetry, showing a significant correlation between absorbed dose to BM and hematological toxicity in 177Lu-DOTATATE treatments. In the present study, they aimed to further evaluate this BM dosimetry method by finding optimal settings for dividing the whole body into two compartments; in terms of minimizing the coefficient of variation (CV) for the individual absorbed doses and studying its correlation to the BM response. The authors have also added specific absorbed fractions for male and female. Finally, they compare this two-compartment method with whole-body dosimetry. METHODS: This study included 46 patients with advanced neuroendocrine tumors treated with 177Lu-DOTATATE on two to five occasions at Sahlgrenska University Hospital. Planar gamma camera images were collected at four time points postinjection, and a segmentation tool using a normalized number of uptake foci (nNUF) to divide the whole body into high- and low-uptake compartments was used. The authors characterized the two-compartment model and compared it with whole-body dosimetry. RESULTS AND CONCLUSION: The dosimetry method was robust, with an optimal nNUF value of 0.1-0.2. Using an nNUF value of 0.15, the absorbed BM dose was estimated as 0.20 Gy/7.4 GBq, and the CV as 8.4%. Compared to whole-body dosimetry, stronger correlation was found between absorbed dose to BM and hematological response using the two-compartment method. The two-compartment method has potential as a valuable image-based alternative to blood-based BM dosimetry.

The added value of ECG-gating for the diagnosis of myocardial infarction using myocardial perfusion scintigraphy and artificial neural networks.

To assess the value of ECG-gating for the diagnosis of myocardial infarction using myocardial perfusion scintigraphy (MPS) and an artificial neural network. A total of 422 patients referred for MPS were studied using a one day (99m)Tc-tetrofosmin protocol. Adenosine stress combined with submaximal dynamic exercise was used. The images were interpreted by one of three experienced clinicians and these interpretations regarding the presence or absence of myocardial infarction were used as the standard. A fully automated method using artificial neural networks was compared with the clinical interpretation. Either perfusion data alone or a combination of perfusion and function from ECG-gated images were used as input to different artificial neural networks. After a training session, the two types of neural networks were evaluated in separate test groups using an eightfold cross-validation procedure. The neural networks trained with both perfusion and ECG-gated images had a 4-7% higher specificity compared with the corresponding networks using perfusion data only, in four of five segments compared at the same level of sensitivity. The greatest improvement in specificity, from 70% to 77%, was seen in the inferior segment. In the septal and lateral segments the specificity rose from 73% to 77% and from 81% to 85%, respectively. In the anterior segment, the increase in specificity from 93% to 94% by adding functional data was not significant. The addition of functional information from ECG-gated MPS is of value for the diagnosis of myocardial infarction using an automated method of interpreting myocardial perfusion images.

IMPROVED PLANAR KIDNEY ACTIVITY CONCENTRATION ESTIMATE BY THE POSTERIOR VIEW METHOD IN 177LU-DOTATATE TREATMENTS.

The aims of this study were to determine how different background regions of interest (ROIs) around the kidney represent true background activity in over- and underlying tissues in (177)Lu-DOTA-octreatate ((177)Lu-DOTATATE) treatments and to determine the influence of the background positions on the kidney activity concentration estimates by the conjugate view (ConjV) and posterior view (PostV) methods. The analysis was performed in single-photon emission computed tomography (SPECT) images of 20 patients, acquired 24 h post injection of a (177)Lu-DOTATATE treatment, by a computer algorithm that created planar images from the SPECT data. The ratio between the activity concentration in the background and the true background varied from 0.36 to 2.08 [coefficient of variation (CV) = 25-181 %] and from 0.44 to 1.52 (CV = 16-70 %) for the right and left kidneys, respectively. The activity concentration estimate in the kidneys was most accurate with the PostV method using a background ROI surrounding the whole kidney, and this combination might be an alternative planar method for improved kidney dosimetry in the (177)Lu-DOTATATE treatments.

Simulation Model of Microsphere Distribution for Selective Internal Radiation Therapy Agrees With Observations.

PURPOSE: To perform a detailed analysis of microsphere distribution in biopsy material from a patient treated with (90)Y-labeled resin spheres and characterize microsphere distribution in the hepatic artery tree, and to construct a novel dichotomous bifurcation model for microsphere deposits and evaluate its accuracy in simulating the observed microsphere deposits. METHODS AND MATERIALS: Our virtual model consisted of arteries that successively branched into 2 new generations of arteries at 20 nodes. The artery diameter exponentially decreased from the lowest generation to the highest generation. Three variable parameters were optimized to obtain concordance between simulations and measure microsphere distributions: an artery coefficient of variation (ACV) for the diameter of all artery generations and the microsphere flow distribution at the nodes; a hepatic tree distribution volume (HDV) for the artery tree; and an artery diameter reduction (ADR) parameter. The model was tested against previously measured activity concentrations in 84 biopsies from the liver of 1 patient. In 16 of 84 biopsies, the microsphere distribution regarding cluster size and localization in the artery tree was determined via light microscopy of 30-µm sections (mean concentration, 14 microspheres/mg; distributions divided into 3 groups with mean microsphere concentrations of 4.6, 14, and 28 microspheres/mg). RESULTS: Single spheres and small clusters were observed in terminal arterioles, whereas large clusters, up to 450 microspheres, were observed in larger arterioles. For 14 microspheres/mg, the optimized parameter values were ACV=0.35, HDV = 50 cm(3), and ADR=6 µm. For 4.6 microspheres/mg, ACV and ADR decreased to 0.26 and 0 µm, respectively, whereas HDV increased to 130 cm(3). The opposite trend was observed for 28 microspheres/mg: ACV = 0.49, HDV = 20 cm(3), and ADR = 8 µm. CONCLUSION: Simulations and measurements reveal that microsphere clusters are larger and more common in volumes with high microsphere concentrations and indicate that the spatial distribution of the artery tree must be considered in estimates of microsphere distributions.

Analytic Validation of the Automated Bone Scan Index as an Imaging Biomarker to Standardize Quantitative Changes in Bone Scans of Patients with Metastatic Prostate Cancer.

UNLABELLED: A reproducible and quantitative imaging biomarker is needed to standardize the evaluation of changes in bone scans of prostate cancer patients with skeletal metastasis. We performed a series of analytic validation studies to evaluate the performance of the automated bone scan index (BSI) as an imaging biomarker in patients with metastatic prostate cancer. METHODS: Three separate analytic studies were performed to evaluate the accuracy, precision, and reproducibility of the automated BSI. Simulation study: bone scan simulations with predefined tumor burdens were created to assess accuracy and precision. Fifty bone scans were simulated with a tumor burden ranging from low to high disease confluence (0.10-13.0 BSI). A second group of 50 scans was divided into 5 subgroups, each containing 10 simulated bone scans, corresponding to BSI values of 0.5, 1.0, 3.0, 5.0, and 10.0. Repeat bone scan study: to assess the reproducibility in a routine clinical setting, 2 repeat bone scans were obtained from metastatic prostate cancer patients after a single 600-MBq (99m)Tc-methylene diphosphonate injection. Follow-up bone scan study: 2 follow-up bone scans of metastatic prostate cancer patients were analyzed to determine the interobserver variability between the automated BSIs and the visual interpretations in assessing changes. The automated BSI was generated using the upgraded EXINI bone(BSI) software (version 2). The results were evaluated using linear regression, Pearson correlation, Cohen κ measurement, coefficient of variation, and SD. RESULTS: Linearity of the automated BSI interpretations in the range of 0.10-13.0 was confirmed, and Pearson correlation was observed at 0.995 (n = 50; 95% confidence interval, 0.99-0.99; P < 0.0001). The mean coefficient of variation was less than 20%. The mean BSI difference between the 2 repeat bone scans of 35 patients was 0.05 (SD = 0.15), with an upper confidence limit of 0.30. The interobserver agreement in the automated BSI interpretations was more consistent (κ = 0.96, P < 0.0001) than the qualitative visual assessment of the changes (κ = 0.70, P < 0.0001) was in the bone scans of 173 patients. CONCLUSION: The automated BSI provides a consistent imaging biomarker capable of standardizing quantitative changes in the bone scans of patients with metastatic prostate cancer.

Left ventricular diastolic dysfunction late after aortic valve replacement in patients with aortic stenosis.

Patients with severe aortic stenosis (AS) are known to have increased left ventricular (LV) mass and diastolic dysfunction. It has been suggested that LV mass and diastolic function normalize after aortic valve replacement (AVR). In the present study, change in LV mass index and diastolic function 10 years after AVR for AS was evaluated. Patients who underwent AVR from 1991 to 1993 (n = 57; mean age 67 +/- 8.6 years at AVR, 58% men) were investigated with Doppler echocardiography preoperatively and 2 and 10 years postoperatively. Diastolic function was evaluated by integrating mitral and pulmonary venous flow data. Expected values for each patient, taking age into consideration, were defined using a control group (n = 71; age range 18 to 83 years). Patients were classified into 4 types: normal diastolic function (type A), mild diastolic dysfunction (type B), moderate diastolic dysfunction (type C), and severe diastolic dysfunction (type D). There was a reduction in LV mass index between the preoperative (161 +/- 39 g/m2) and 2-year follow-up (114 +/- 28 g/m2) examinations (p <0.0001), but no further reduction was seen at 10 years (119 +/- 49 g/m2). The percentage of patients with increased LV mass index decreased from 83% preoperatively to 29% at 2-year follow-up (p <0.001). The percentage of patients with moderate to severe LV diastolic dysfunction (types C and D) was unchanged between the preoperative (7%) and 2-year follow-up (13%) examinations (p = 0.27). The percentage of patients increased at 10-year follow-up to 61% (p <0.0001). In conclusion, this reveals the development of moderate to severe diastolic dysfunction 10 years after AVR, despite a reduction in the LV mass index.

Preoperative moderate to severe diastolic dysfunction: a novel Doppler echocardiographic long-term prognostic factor in patients with severe aortic stenosis.

OBJECTIVE: We studied long-term outcomes in severe aortic stenosis and the importance of prosthesis type (mechanical vs biologic) and size, preoperative left ventricular ejection fraction, diastolic function, and left ventricular mass. METHODS: Patients undergoing valve replacement from 1991 to 1993 (n = 399, 45% women) were included. The diastolic function was evaluated by integrating mitral and pulmonary venous flow data with Doppler echocardiography. The patients were classified as having either normal diastolic function to mild diastolic dysfunction or moderate to severe diastolic dysfunction. Left ventricular ejection fraction and the diastolic function category were incorporated together with age, sex, and time since operation into a Poisson regression model with death as the end point. Prosthesis type and size and left ventricular mass were also investigated. RESULTS: The age (mean +/- SD) was 71 +/- 9 years, and the overall survival after 12 years was 50%. Although markedly reduced during the initial 6-month period, mortality risk subsequently increased more than could be explained by age (hazard ratio of 1-year difference = 1.12, P = .0005). The moderate to severe diastolic dysfunction pattern independently predicted late mortality (hazard ratio = 1.72, P = .0038), whereas left ventricular ejection fraction did not (hazard ratio = 0.99, P = .18). The prognostic importance of moderate to severe diastolic dysfunction did not diminish with time; on the contrary, it tended to increase. Mortality after 12 years was not predicted by left ventricular mass (P = .66), prosthesis type (P = .57), or prosthesis size (P = .58). CONCLUSION: This study reveals that moderate to severe diastolic dysfunction in patients with aortic stenosis is an independent predictor of late mortality after valve replacement and that its importance does not decrease with time. Our findings may suggest that moderate to severe diastolic dysfunction implies nonreversible myocardial changes that negatively affect survival.

Increased absorbed liver dose in Selective Internal Radiation Therapy (SIRT) correlates with increased sphere-cluster frequency and absorbed dose inhomogeneity.

BACKGROUND: The higher tolerated mean absorbed dose for selective internal radiation therapy (SIRT) with intra-arterially infused (90)Y microspheres compared to external beam therapy is speculated to be caused by absorbed dose inhomogeneity, which allows for liver regeneration. However, the complex liver microanatomy and rheology makes modelling less valuable if the tolerance doses are not based on the actual microsphere distribution. The present study demonstrates the sphere distribution and small-scale absorbed dose inhomogeneity and its correlation with the mean absorbed dose in liver tissue resected after SIRT. METHODS: A patient with marginally resectable cholangiocarcinoma underwent SIRT 9 days prior to resection including adjacent normal liver tissue. The resected specimen was formalin-fixed and sliced into 1 to 2-mm sections. Forty-one normal liver biopsies 6-8 mm in diameter were punched from these sections and the radioactivity measured. Sixteen biopsies were further processed for detailed analyses by consecutive serial sectioning of 15 30-µm sections per biopsy, mounted and stained with haematoxylin-eosin. All sections were scrutinised for isolated or conglomerate spheres. Small-scale dose distributions were obtained by applying a (90)Y-dose point kernel to the microsphere distributions. RESULTS: A total of 3888 spheres were found in the 240 sections. Clusters were frequently found as strings in the arterioles and as conglomerates in small arteries, with the largest cluster comprising 453 spheres. An increased mean absorbed dose in the punch biopsies correlated with large clusters and a greater coefficient of variation. In simulations the absorbed dose was 5-1240 Gy; 90% were 10-97 Gy and 45% were <30 Gy, the assumed tolerance in external beam therapy. CONCLUSIONS: Sphere clusters were located in both arterioles and small arteries and increased in size with increasing sphere concentration, resulting in increased absorbed dose inhomogeneity, which contradicts earlier modelling studies.