Effects of exercise and airway clearance (positive expiratory pressure) on mucus clearance in cystic fibrosis: a randomised crossover trial.

Exercise improves mucus clearance in people without lung disease and those with chronic bronchitis. No study has investigated exercise alone for mucus clearance in cystic fibrosis (CF). The aim of this study was to compare the effects of treadmill exercise to resting breathing and airway clearance with positive expiratory pressure (PEP) therapy on mucus clearance in adults with CF.This 3-day randomised, controlled, crossover trial included 14 adults with mild to severe CF lung disease (forced expiratory volume in 1 s % predicted 31-113%). Interventions were 20 min of resting breathing (control), treadmill exercise at 60% of the participant's peak oxygen consumption or PEP therapy (including huffing and coughing). Mucus clearance was measured using the radioaerosol technique and gamma camera imaging.Treadmill exercise improved whole lung mucus clearance compared to resting breathing (mean difference 3%, 95% CI 2-4); however, exercise alone was less effective than PEP therapy (mean difference -7%, 95% CI -6- -8). When comparing treadmill exercise to PEP therapy, there were no significant differences in mucus clearance from the intermediate and peripheral lung regions, but significantly less clearance from the central lung region (likely reflecting the huffing and coughing that was only in PEP therapy).It is recommended that huffing and coughing are included to maximise mucus clearance with exercise.

Side lying during nebulisation can significantly improve apical deposition in healthy adults and adults with mild cystic fibrosis lung disease: a randomised crossover trial.

BACKGROUND: In people with and without Cystic Fibrosis (CF), does side lying during nebulisation change: the proportion of the dose loaded in the nebuliser that is deposited in the lungs; the uniformity of deposition throughout the lungs; or the apical drug density as a percentage of the drug density in the remaining lung? Do these effects differ depending on the degree of lung disease present? METHODS: A randomised crossover trial with concealed allocation, intention-to-treat analysis and blinded assessors, involving 39 adults: 13 healthy, 13 with mild CF lung disease (FEV1 > 80%pred), and 13 with more advanced CF lung disease (FEV1 < 80%pred). In random order, 4 mL of nebulised radioaerosol was inhaled in upright sitting and in alternate right and left side lying at 2-min intervals, for 20 min. RESULTS: Compared to sitting upright, lung deposition and the uniformity of deposition were not significantly altered by side lying in any of the three groups. In sitting, the density of the deposition was significantly less in the apical regions than in the rest of the lung in all participants. Side lying significantly improved apical deposition in healthy adults (MD, 13%; 95% CI, 7 to 19), and in minimal CF lung disease (MD, 4%; 95% CI, 1 to 7) but not in advanced disease (MD, 4%; 95% CI, - 2 to 9). CONCLUSION: Alternating between right and left side lying during nebulisation significantly improves apical deposition in healthy adults and in adults with mild CF lung disease, without substantial detriment to overall deposition. TRIAL REGISTRATION: ACTRN12611000674932 (Healthy), ACTRN12611000672954 (CF) Retrospectively registered 4/7/2011.

The relationship between neuropsychological functioning and FDG-PET hypometabolism in intractable mesial temporal lobe epilepsy.

We examined the relationship between baseline neuropsychological functioning and 18-fluorodeoxyglucose positron emission tomography (FDG-PET) in intractable mesial temporal lobe epilepsy (MTLE). We hypothesized relationships between dominant temporal lobe hypometabolism and verbal memory and between nondominant temporal lobe hypometabolism and nonverbal memory in line with the lateralized material-specific model of memory deficits in MTLE. We also hypothesized an association between performance on frontal lobe neuropsychological tests and prefrontal hypometabolism. Thirty-two patients who had undergone temporal lobectomy for treatment of MTLE and who completed both presurgical FDG-PET and comprehensive neuropsychological investigations with widely used standardized measures were included. Age-adjusted composite measures were calculated for verbal memory, nonverbal memory, relative material-specific memory, IQ, executive function, attention/working memory, and psychomotor speed. Fluorodeoxyglucose positron emission tomography was analyzed with statistical parametric mapping (SPM) to identify hypometabolism relative to healthy controls. Pearson's correlation was used to determine the relationship between regions of hypometabolism and neuropsychological functioning. Dominant temporal lobe hypometabolism was associated with relatively inferior verbal memory, while nondominant temporal lobe hypometabolism was associated with inferior nonverbal memory. No relationship was found between performance on any frontal lobe measures and prefrontal hypometabolism. Statistical parametric mapping-quantified lateralized temporal lobe hypometabolism correlates with material-specific episodic memory impairment in MTLE. In contrast, prefrontal hypometabolism is not associated with performance on frontal lobe measures. We suggest that this is because frontal lobe neuropsychology tests may not be good measures of isolated frontal lobe functioning.

The cognitive profile of occipital lobe epilepsy and the selective association of left temporal lobe hypometabolism with verbal memory impairment.

We investigated the cognitive profile of structural occipital lobe epilepsy (OLE) and whether verbal memory impairment is selectively associated with left temporal lobe hypometabolism on [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET). Nine patients with OLE, ages 8-29 years, completed presurgical neuropsychological assessment. Composite measures were calculated for intelligence quotient (IQ), speed, attention, verbal memory, nonverbal memory, and executive functioning. In addition, the Wisconsin Card Sorting Test (WCST) was used as a specific measure of frontal lobe functioning. Presurgical FDG-PET was analyzed with statistical parametric mapping in 8 patients relative to 16 healthy volunteers. Mild impairments were evident for IQ, speed, attention, and executive functioning. Four patients demonstrated moderate or severe verbal memory impairment. Temporal lobe hypometabolism was found in seven of eight patients. Poorer verbal memory was associated with left temporal lobe hypometabolism (p = 0.002), which was stronger (p = 0.03 and p = 0.005, respectively) than the association of left temporal lobe hypometabolism with executive functioning or with performance on the WCST. OLE is associated with widespread cognitive comorbidity, suggesting cortical dysfunction beyond the occipital lobe. Verbal memory impairment is selectively associated with left temporal lobe hypometabolism in OLE, supporting a link between neuropsychological dysfunction and remote hypometabolism in focal epilepsy.

Relationship between preoperative hypometabolism and surgical outcome in neocortical epilepsy surgery.

PURPOSE: Fluorine-18-fluorodeoxyglucose-positron emission tomography (FDG-PET) hypometabolism has been used to localize the epileptogenic zone. However, glucose hypometabolism remote to the ictal focus is common and its relationship to surgical outcome has not been considered in many studies. We investigated the relationship between surgical outcome and FDG-PET hypometabolism topography in a large cohort of patients with neocortical epilepsy. METHODS: We identified all patients (n = 68) who had interictal FDG-PET between 1994 and 2004 and who underwent resective epilepsy surgery with follow up for more than 2 years. The volumes of significant FDG-PET hypometabolism involving the resected epileptic focus and its surrounding regions (perifocal hypometabolism) and those distant to and not contiguous with the perifocal hypometabolism (remote hypometabolism) were determined statistically using Statistical Parametric Mapping (voxel threshold p = 0.01, extent threshold ≥ 250 voxels, uncorrected cluster-level significance p < 0.05) and were compared with magnetic resonance imaging (MRI) and clinical and demographic variables using a multiple logistic regression model to identify independent predictors of seizure outcome. KEY FINDINGS: Remote hypometabolism was present in 39 patients. Seizure freedom was 49% (19 of 39 patients) in patients with glucose hypometabolism remote from the epileptogenic zone compared to 90% (26 of 29 patients) in patients without remote hypometabolism. In 43 patients with an MRI-identified lesion, seizure freedom was 79% (34 of 43 patients). In patients with normal MRI, cortical dysplasia was the predominant pathologic substrate. Multiple logistic regression analysis identified a larger volume of significant remote hypometabolism (p < 0.005) and absence of a MRI-localized lesion (p = 0.006) as independent predictors of continued seizures after surgery. SIGNIFICANCE: In patients with widespread glucose hypometabolism that is statistically significant when compared to controls, epilepsy surgery may not result in complete seizure freedom despite complete removal of the MRI-identified lesion. The volume of significant glucose hypometabolism remote to the ictal-onset zone may be an independent predictor of the success of epilepsy surgery.

Synthesis of 68Ga-radiopharmaceuticals using both generator-derived and cyclotron-produced 68Ga as exemplified by [68Ga]Ga-PSMA-11 for prostate cancer PET imaging.

[68Ga]Ga-PSMA-11, a urea-based peptidomimetic, is a diagnostic radiopharmaceutical for positron emission tomography (PET) imaging that targets the prostate-specific membrane antigen (PSMA). The recent Food and Drug Administration approval of [68Ga]Ga-PSMA-11 for PET imaging of patients with prostate cancer, expected follow-up approval of companion radiotherapeutics (e.g., [177Lu]Lu-PSMA-617, [225Ac]Ac-PSMA-617) and large prostate cancer patient volumes requiring access are poised to create an unprecedented demand for [68Ga]Ga-PSMA-11 in nuclear medicine clinics around the world. Meeting this global demand is going to require a variety of synthesis methods compatible with 68Ga eluted from a generator or produced on a cyclotron. To address this urgent need in the PET radiochemistry community, herein we report detailed protocols for the synthesis of [68Ga]Ga-PSMA-11, (also known as HBED-CC, Glu-urea-Lys(Ahx)-HBED-CC and PSMA-HBED-CC) using both generator-eluted and cyclotron-produced 68Ga and contrast the pros and cons of each method. The radiosyntheses are automated and have been validated for human use at two sites (University of Michigan (UM), United States; Royal Prince Alfred Hospital (RPA), Australia) and used to produce [68Ga]Ga-PSMA-11 for patient use in good activity yields (single generator, 0.52 GBq (14 mCi); dual generators, 1.04-1.57 GBq (28-42 mCi); cyclotron method (single target), 1.47-1.89 GBq (40-51 mCi); cyclotron method (dual target), 3.63 GBq (98 mCi)) and high radiochemical purity (99%) (UM, n = 645; RPA, n > 600). Both methods are appropriate for clinical production but, in the long term, the method employing cyclotron-produced 68Ga is the most promising for meeting high patient volumes. Quality control testing (visual inspection, pH, radiochemical purity and identity, radionuclidic purity and identity, sterile filter integrity, bacterial endotoxin content, sterility, stability) confirmed doses are suitable for clinical use, and there is no difference in clinical prostate cancer PET imaging using [68Ga]Ga-PSMA-11 prepared using the two production methods.

The topography and significance of extratemporal hypometabolism in refractory mesial temporal lobe epilepsy examined by FDG-PET.

PURPOSE: This study aims to map the temporal and extratemporal 18-fluorodeoxyglucose positron emission tomography (FDG-PET)-defined hypometabolism in mesial temporal lobe epilepsy (MTLE). We hypothesize that quantitative analysis will reveal extensive extratemporal glucose hypometabolism (EH), that the EH is related to seizure propagation beyond the temporal lobe, hypometabolism restricted to one temporal lobe predicts a good outcome following surgery, and EH predicts a poor outcome. METHODS: Sixty-four patients were studied who had undergone temporal lobectomy for intractable MTLE and had at least 2 years of postoperative follow-up. Spatial preprocessing and statistical analysis on preoperative interictal FDG-PET using statistical parametric mapping (SPM 2) identified significant regions of hypometabolism compared to normal controls. The predictors of outcome were determined by univariable and multiple logistic regression analyses. RESULTS: EH was common and widespread, occurring most frequently in the ipsilateral insula and frontal lobe. The extent of EH was not significantly associated with age of onset or the duration of epilepsy. Presence of secondarily generalized tonic--clonic seizures (SGTCS) was associated with a larger extent of remote hypometabolism (RH, p < 0.005). Multiple logistic regression analysis identified the extent of RH and the age at surgery as independent predictors of seizure outcome. DISCUSSION: Our results indicate that RH in MTLE is associated with a poorer surgical outcome, especially if seen in the contralateral hemisphere. The extent of RH relates to SGTCS but not to duration of epilepsy.

NEMA NU 2-2001 performance testing of a Philips Gemini GXL PET/CT scanner.

Post installation acceptance testing is vital to demonstrate that the equipment meets the vendor's specification and is suitable for clinical studies. The test procedures described in the NEMA NU 2-2001 document form the basis of vendor performance specifications of PET scanners and hence are also appropriate for acceptance testing. Initial installation performance tests of the Philips Gemini GXL PET/CT scanner installed at Liverpool Hospital revealed that the peak noise equivalent count rate (NECR) measurement of 57.5 kcps was substantially lower than the specification of 70 kcps and the scatter fraction of 38.5% was 10% higher than the specification of

Cyclotron-based production of 68Ga, [68Ga]GaCl3, and [68Ga]Ga-PSMA-11 from a liquid target.

PURPOSE: To optimize the direct production of 68Ga on a cyclotron, via the 68Zn(p,n)68Ga reaction using a liquid cyclotron target. We Investigated the yield of cyclotron-produced 68Ga, extraction of [68Ga]GaCl3 and subsequent [68Ga]Ga-PSMA-11 labeling using an automated synthesis module. METHODS: Irradiations of a 1.0 M solution of [68Zn]Zn(NO3)2 in dilute (0.2-0.3 M) HNO3 were conducted using GE PETtrace cyclotrons and GE 68Ga liquid targets. The proton beam energy was degraded to a nominal 14.3 MeV to minimize the co-production of 67Ga through the 68Zn(p,2n)67Ga reaction without unduly compromising 68Ga yields. We also evaluated the effects of varying beam times (50-75 min) and beam currents (27-40 µA). Crude 68Ga production was measured. The extraction of [68Ga]GaCl3 was performed using a 2 column solid phase method on the GE FASTlab Developer platform. Extracted [68Ga]GaCl3 was used to label [68Ga]Ga-PSMA-11 that was intended for clinical use. RESULTS: The decay corrected yield of 68Ga at EOB was typically > 3.7 GBq (100 mCi) for a 60 min beam, with irradiations of [68Zn]Zn(NO3)2 at 0.3 M HNO3. Target/chemistry performance was more consistent when compared with 0.2 M HNO3. Radionuclidic purity of 68Ga was typically > 99.8% at EOB and met the requirements specified in the European Pharmacopoeia (< 2% combined 66/67Ga) for a practical clinical product shelf-life. The activity yield of [68Ga]GaCl3 was typically > 50% (~ 1.85 GBq, 50 mCi); yields improved as processes were optimized. Labeling yields for [68Ga]Ga-PSMA-11 were near quantitative (~ 1.67 GBq, 45 mCi) at EOS. Cyclotron produced [68Ga]Ga-PSMA-11 underwent full quality control, stability and sterility testing, and was implemented for human use at the University of Michigan as an Investigational New Drug through the US FDA and also at the Royal Prince Alfred Hospital (RPA). CONCLUSION: Direct cyclotron irradiation of a liquid target provides clinically relevant quantities of [68Ga]Ga-PSMA-11 and is a viable alternative to traditional 68Ge/68Ga generators.

Effect of particle size of dry powder mannitol on the lung deposition in healthy volunteers.

There is a lack of in vivo studies focusing on the effect of particle size of dry powder aerosols on lung deposition and distribution. We investigated the dose and distribution of radiolabelled powder aerosols of mannitol in the lungs using single photon emission tomography (SPECT). Three different sized radiolabelled powders were produced by co-spray drying mannitol with 99mTc-DTPA. The primary particle size distribution of the powders measured by laser diffraction showed a volume median diameter of 2, 3 and 4 microm with span 2.3, 2.0 and 2.1, respectively, which corresponded to an aerodynamic diameter of 2.7, 3.6, 5.4 microm and geometric standard deviation of 2.6, 2.4 and 2.7 when the powders were dispersed using an Aeroliser dry powder inhaler. Three capsules each containing approximately 20mg (i.e. a total of 60 mg containing 60-90 MBq) of each of the radiolabelled powders were inhaled by eight healthy volunteers using the Aeroliser inhaler. Images of aerosol deposition in the lungs were acquired using fast, multi-bed position SPECT. The lung dose markedly decreased with increasing aerosol particle size (mean+/-S.E.M.: 44.8+/-2.4, 38.9+/-0.9, 20.6+/-1.6% for 2.7, 3.6, 5.4 microm, respectively, p<0.0001). The sites of deposition of the 2.7 and 3.6 microm aerosols were similar (penetration index, PI=0.63+/-0.05, 0.60+/-0.03, respectively, p>0.3), but different to the 5.4 microm aerosols (PI=0.52+/-0.04, p<0.02). The lung dose followed the in vitro powder dispersion performance, with the % lung dose being related to fine particle fraction by a slope of 0.8 for a regression with intercepts forced through the origin. The SPECT results provide direct evidence that the lung deposition of dry powder aerosols depends on the particle size. The lung dose of the 2.7 and 3.6 microm aerosols using the Aeroliser was double compared to that of the 5.4 microm aerosols and the deposition of the smaller particles was more peripheral.

Enhanced parameter estimation methods for noisy SPECT data.

Functional imaging with PET and SPECT is capable of visualizing subtle changes in physiological function in vivo, which aids in the early diagnosis of disease. Quantitative functional parameters are usually derived by curve fitting the dynamic data of a functional imaging study. However, the intrinsic high level of noise and low signal to noise ratio can lead to instability in the parameter estimation and give rise to non-physiological parameter estimates. Clustering techniques have been applied to improve signal to noise ratio and the reliability of parametric image generation, but these may enhance partial volume effects (PVE) and result in biased estimates for small structures. Therefore, a systematic study was performed using computer simulations of SPECT data and the generalized linear least square algorithm (GLLS) to evaluate the ability of three proposed enhanced methods and a clustering-aided method to improve the reliability of parametric image generation. The results demonstrate that clustering with sufficient cluster numbers ameliorated PVE and provided noise-insensitive parameter estimates. The enhanced GLLS method with a prior volume of distribution and bootstrap Monte Carlo resampling improved the reliability of the curve fitting, and is thus suitable for application to noisy SPECT data.

A topo-graph model for indistinct target boundary definition from anatomical images.

BACKGROUND AND OBJECTIVE: It can be challenging to delineate the target object in anatomical imaging when the object boundaries are difficult to discern due to the low contrast or overlapping intensity distributions from adjacent tissues. METHODS: We propose a topo-graph model to address this issue. The first step is to extract a topographic representation that reflects multiple levels of topographic information in an input image. We then define two types of node connections - nesting branches (NBs) and geodesic edges (GEs). NBs connect nodes corresponding to initial topographic regions and GEs link the nodes at a detailed level. The weights for NBs are defined to measure the similarity of regional appearance, and weights for GEs are defined with geodesic and local constraints. NBs contribute to the separation of topographic regions and the GEs assist the delineation of uncertain boundaries. Final segmentation is achieved by calculating the relevance of the unlabeled nodes to the labels by the optimization of a graph-based energy function. We test our model on 47 low contrast CT studies of patients with non-small cell lung cancer (NSCLC), 10 contrast-enhanced CT liver cases and 50 breast and abdominal ultrasound images. The validation criteria are the Dice's similarity coefficient and the Hausdorff distance. RESULTS: Student's t-test show that our model outperformed the graph models with pixel-only, pixel and regional, neighboring and radial connections (p-values <0.05). CONCLUSIONS: Our findings show that the topographic representation and topo-graph model provides improved delineation and separation of objects from adjacent tissues compared to the tested models.

Fast and reliable estimation of multiple parametric images using an integrated method for dynamic SPECT.

Dynamic single photon emission computed tomography (SPECT) has demonstrated the potential to quantitatively estimate physiological parameters in the brain and the heart. The generalized linear least square (GLLS) method is a well-established method for solving linear compartment models with fast computational speed. However, the high level of noise intrinsic in the SPECT data leads to reliability and instability problems of GLLS for generating parametric images. An integrated method is proposed to restrict the noise in both the temporal and spatial domains to estimate multiple parametric images for dynamic SPECT. This method comprises three steps which are optimum image sampling schedule in the projection space, cluster analysis applied postreconstruction and parametric image generation with GLLS. The simulation and experimental studies for the neuronal nicotine acetylcholine receptor tracer of 5-[123I]-iodo-A-85380 were employed to evaluate the performance of the proposed method. The results of influx rate of K1 and volume of distribution of Vd demonstrated that the integrated method was successful in generating low noise parametric images for high noise SPECT data without enhancing the partial volume effect. Furthermore, the integrated method is computationally efficient for potential clinical applications.

Real-time volume rendering visualization of dual-modality PET/CT images with interactive fuzzy thresholding segmentation.

Three-dimensional (3-D) visualization has become an essential part for imaging applications, including image-guided surgery, radiotherapy planning, and computer-aided diagnosis. In the visualization of dual-modality positron emission tomography and computed tomography (PET/CT), 3-D volume rendering is often limited to rendering of a single image volume and by high computational demand. Furthermore, incorporation of segmentation in volume rendering is usually restricted to visualizing the presegmented volumes of interest. In this paper, we investigated the integration of interactive segmentation into real-time volume rendering of dual-modality PET/CT images. We present and validate a fuzzy thresholding segmentation technique based on fuzzy cluster analysis, which allows interactive and real-time optimization of the segmentation results. This technique is then incorporated into a real-time multi-volume rendering of PET/CT images. Our method allows a real-time fusion and interchangeability of segmentation volume with PET or CT volumes, as well as the usual fusion of PET/CT volumes. Volume manipulations such as window level adjustments and lookup table can be applied to individual volumes, which are then fused together in real time as adjustments are made. We demonstrate the benefit of our method in integrating segmentation with volume rendering in its application to PET/CT images. Responsive frame rates are achieved by utilizing a texture-based volume rendering algorithm and the rapid transfer capability of the high-memory bandwidth available in low-cost graphic hardware.

SPECT Imaging for Radioaerosol Deposition and Clearance Studies.

Planar gamma camera scintigraphy is well established for measuring the deposition and clearance of radioaerosols. Single photon emission computed tomography (SPECT) provides threedimensional (3D) reconstructions of the radioactivity distribution, thus avoiding the compression of 3D data into two-dimensional (2D) images and potentially offering superior assessment of aerosol deposition patterns. However, SPECT has traditionally been associated with long imaging times, making it unsuitable for measuring deposition and clearance of radioaerosols with fast clearance. Multi-detector SPECT systems can collect complete SPECT studies in <1 min, allowing both initial deposition and clearance over time to be assessed by dynamic SPECT. Simultaneous transmission measurement with an external source provides attenuation correction for absolute activity quantification as well as aiding in the definition of the lung volume of interest. A dynamic SPECT imaging protocol has been developed to allow fast imaging from the oropharynx to the abdomen using gamma cameras with limited axial field of views. This allows activity quantification not only in the lungs, but also in areas outside the thorax. However, fast dynamic SPECT imaging is technically and computationally more demanding and provides less scope for reducing the radioactivity administered to the subjects. It has been shown that dynamic SPECT, compared to planar imaging, is more sensitive in detecting changes in deposition as measured by the Penetration Index (PI). Thus, SPECT can better differentiate between large and small airways, which is important for lung regional analysis.

Lung deposition of mannitol powder aerosol in healthy subjects.

Mannitol as a dry powder aerosol is used for bronchoprovocation testing and to enhance mucus clearance in people with excessive airway secretions. The dose and distribution of the deposited aerosol in the lung was investigated using fast single photon emission tomography (SPECT) imaging. Mannitol powder (3 microm particle size) was produced by spray drying and radiolabeled with (99m)Tc-DTPA. Approximately 60 mg of radiolabeled mannitol (containing 52-68 MBq of (99m)Tc-DTPA) was administered to 10 healthy subjects using the Inhalator dry powder inhaler (DPI), and SPECT images (1 min each) were collected. Thirteen percent to 31% of the dose of mannitol loaded in the inhaler deposited in the lungs and the deposited dose correlated positively with the peak inhalation air flow. The regional aerosol lung distribution, as expressed by the penetration index (i.e., ratio of peripheral to central deposition in the lung) varied from 0.31 to 0.88, which however showed no dependency on any flow parameters. The variation in response to the same dose of mannitol within the asthmatic population may in part be explained by these findings.

Segmentation of VOI from multidimensional dynamic PET images by integrating spatial and temporal features.

Segmentation of multidimensional dynamic positron emission tomography (PET) images into volumes of interest (VOIs) exhibiting similar temporal behavior and spatial features is a challenging task due to inherently poor signal-to-noise ratio and spatial resolution. In this study, we propose VOI segmentation of dynamic PET images by utilizing both the three-dimensional (3-D) spatial and temporal domain information in a hybrid technique that integrates two independent segmentation techniques of cluster analysis and region growing. The proposed technique starts with a cluster analysis that partitions the image based on temporal similarities. The resulting temporal partitions, together with the 3-D spatial information are utilized in the region growing segmentation. The technique was evaluated with dynamic 2-[18F] fluoro-2-deoxy-D-glucose PET simulations and clinical studies of the human brain and compared with the k-means and fuzzy c-means cluster analysis segmentation methods. The quantitative evaluation with simulated images demonstrated that the proposed technique can segment the dynamic PET images into VOIs of different kinetic structures and outperforms the cluster analysis approaches with notable improvements in the smoothness of the segmented VOIs with fewer disconnected or spurious segmentation clusters. In clinical studies, the hybrid technique was only superior to the other techniques in segmenting the white matter. In the gray matter segmentation, the other technique tended to perform slightly better than the hybrid technique, but the differences did not reach significance. The hybrid technique generally formed smoother VOIs with better separation of the background. Overall, the proposed technique demonstrated potential usefulness in the diagnosis and evaluation of dynamic PET neurological imaging studies.

A combinatorial Bayesian and Dirichlet model for prostate MR image segmentation using probabilistic image features.

Blurred boundaries and heterogeneous intensities make accurate prostate MR image segmentation problematic. To improve prostate MR image segmentation we suggest an approach that includes: (a) an image patch division method to partition the prostate into homogeneous segments for feature extraction; (b) an image feature formulation and classification method, using the relevance vector machine, to provide probabilistic prior knowledge for graph energy construction; (c) a graph energy formulation scheme with Bayesian priors and Dirichlet graph energy and (d) a non-iterative graph energy minimization scheme, based on matrix differentiation, to perform the probabilistic pixel membership optimization. The segmentation output was obtained by assigning pixels with foreground and background labels based on derived membership probabilities. We evaluated our approach on the PROMISE-12 dataset with 50 prostate MR image volumes. Our approach achieved a mean dice similarity coefficient (DSC) of 0.90 ± 0.02, which surpassed the five best prior-based methods in the PROMISE-12 segmentation challenge.

Primary lung tumor segmentation from PET-CT volumes with spatial-topological constraint.

PURPOSE: Accurate lung tumor segmentation is a prerequisite for effective radiation therapy and surgical planning. However, tumor delineation is challenging when the tumor boundaries are indistinct on PET or CT. To address this problem, we developed a segmentation method to improve the delineation of primary lung tumors from PET-CT images. METHODS: We formulated the segmentation problem as a label information propagation process in an iterative manner. Our model incorporates spatial-topological information from PET and local intensity changes from CT. The topological information of the regions was extracted based on the metabolic activity of different tissues. The spatial-topological information moderates the amount of label information that a pixel receives: The label information attenuates as the spatial distance increases and when crossing different topological regions. Thus, the spatial-topological constraint assists accurate tumor delineation and separation. The label information propagation and transition model are solved under a random walk framework. RESULTS: Our method achieved an average DSC of 0.848 ± 0.036 and HD (mm) of 8.652 ± 4.532 on 40 patients with lung cancer. The t test showed a significant improvement (p value < 0.05) in segmentation accuracy when compared to eight other methods. Our method was better able to delineate tumors that had heterogeneous FDG uptake and which abutted adjacent structures that had similar densities. CONCLUSIONS: Our method, using a spatial-topological constraint, provided better lung tumor delineation, in particular, when the tumor involved or abutted the chest wall and the mediastinum.

The effect of device resistance and inhalation flow rate on the lung deposition of orally inhaled mannitol dry powder.

The present study investigates the effect of DPI resistance and inhalation flow rates on the lung deposition of orally inhaled mannitol dry powder. Mannitol powder radiolabeled with 99mTc-DTPA was inhaled from an Osmohaler™ by healthy human volunteers at 50-70L/min peak inhalation flow rate (PIFR) using both a low and high resistance Osmohaler™, and 110-130L/min PIFR using the low resistance Osmohaler™ (n=9). At 50-70L/min PIFR, the resistance of the Osmohaler™ did not significantly affect the total and peripheral lung deposition of inhaled mannitol [for low resistance Osmohaler™, 20% total lung deposition (TLD), 0.3 penetration index (PI); for high resistance Osmohaler™, 17% TLD, 0.23 PI]. Increasing the PIFR 50-70L/min to 110-130L/min (low resistance Osmohaler™) significantly reduced the total lung deposition (10% TLD) and the peripheral lung deposition (PI 0.21). The total lung deposition showed dependency on the in vitro FPF (R2=1.0). On the other hand, the PI had a stronger association with the MMAD (R2=1.0) than the FPF (R2=0.7). In conclusion the resistance of Osmohaler™ did not significantly affect the total and regional lung deposition at 50-70L/min PIFR. Instead, the total and regional lung depositions are dependent on the particle size of the aerosol and inhalation flow rate, the latter itself affecting the particle size distribution.