Jonathan Carney

Method for transforming CT images for attenuation correction in PET/CT imaging

A tube-voltage-dependent scheme is presented for transforming Hounsfield units (HU) measured by different computed tomography (CT) scanners at different x-ray tube voltages (kVp) to 511 keV linear attenuation values for attenuation correction in positron emission tomography (PET) data reconstruction. A Gammex 467 electron density CT phantom was imaged using a Siemens Sensation 16-slice CT, a Siemens Emotion 6-slice CT, a GE Lightspeed 16-slice CT, a Hitachi CXR 4-slice CT, and a Toshiba Aquilion 16-slice CT at kVp ranging from 80 to 140 kVp. All of these CT scanners are also available in combination with a PET scanner as a PET/CT tomograph. HU obtained for various reference tissue substitutes in the phantom were compared with the known linear attenuation values at 511 keV. The transformation, appropriate for lung, soft tissue, and bone, yields the function 9.6 x 10(-5). (HU+ 1000) below a threshold of approximately 50 HU and a (HU+ 1000)+b above the threshold, where a and b are fixed parameters that depend on the kVp setting. The use of the kVp-dependent scaling procedure leads to a significant improvement in reconstructed PET activity levels in phantom measurements, resolving errors of almost 40% otherwise seen for the case of dense bone phantoms at 80 kVp. Results are also presented for patient studies involving multiple CT scans at different kVp settings, which should all lead to the same 511 keV linear attenuation values. A linear fit to values obtained from 140 kVp CT images using the kVp-dependent scaling plotted as a function of the corresponding values obtained from 80 kVp CT images yielded y = 1.003 x -0.001 with an R2 value of 0.999, indicating that the same values are obtained to a high degree of accuracy.

Radiologic Responses in Cynomolgus Macaques for Assessing Tuberculosis Chemotherapy Regimens

ABSTRACT Trials to test new drugs currently in development against tuberculosis in humans are impractical. All animal models to prioritize new regimens are imperfect, but nonhuman primates (NHPs) infected with Mycobacterium tuberculosis develop active tuberculosis (TB) disease with a full spectrum of lesion types seen in humans. Serial 2-deoxy-2-[18F]-fluoro-d-glucose (FDG) positron emission tomography (PET) with computed tomography (CT) imaging was performed on cynomolgus macaques during infection and chemotherapy with individual agents or the four-drug combination therapy most widely used globally. The size and metabolic activity of lung granulomas varied among animals and even within a single animal during development of disease. Individual granulomas within untreated animals had highly local and independent outcomes, some progressing in size and FDG uptake, while others waned, illustrating the highly dynamic nature of active TB. At necropsy, even untreated animals were found to have a proportion of sterile lesions consistent with the dynamics of this infection. A more marked reduction in overall metabolic activity in the lungs (decreased FDG uptake) was associated with effective treatment. A reduction in the size of individual lesions correlated with a lower bacterial burden at necropsy. Isoniazid treatment was associated with a transient increase in metabolic activity in individual lesions, whereas a net reduction occurred in most lesions from rifampin-treated animals. Quadruple-drug therapy resulted in the highest decrease in FDG uptake. The findings of PET-CT imaging may provide an important early correlate of the efficacy of novel combinations of new drugs that can be directly translated to human clinical trials.

Image-guided cancer therapy using PET/CT.

Functional imaging with positron emission tomography (PET) is playing an increasingly important role in the diagnosis and staging of malignant disease, image-guided therapy planning, and treatment monitoring. PET scanning with the radiolabeled glucose analogue 18F-fluorodeoxyglucose (18FDG) is a relatively recent addition to the clinically available technology for imaging cancer, complementing the more conventional anatomical imaging modalities of computed tomography (CT) and magnetic resonance (MR). These modalities are complementary in the sense that CT provides accurate localization of organs and lesions while PET maps both normal and abnormal tissue function. When combined, the two modalities can identify and localize functional abnormalities. Attempts to align CT and PET data sets with fusion software are generally successful in the brain, whereas the remainder of the body is more challenging owing to the increased number of possible degrees of freedom between the two scans. Recently these challenges have been addressed by the introduction of the combined PET/CT scanner, a hardware-oriented approach to image fusion. With this device, accurately registered anatomical and functional images can be acquired for each patient in a single scanning session. Currently, over 400 combined PET/CT scanners are installed in medical institutions worldwide, almost all of them for the diagnosis and staging of malignant disease. However, the real impact of this technology undoubtedly will be for cancer therapy, where PET/CT images will be used to guide biopsies and assist in surgical intervention, to define target volumes for radiation therapy and optimize dose, and to monitor response to chemotherapy and establish individualized patient treatment strategies

A method for calibrating the CT-based attenuation correction of PET in human tissue

The use of x-ray computed tomography (CT)-based attenuation correction for positron emission tomography (PET) in PET/CT systems requires the transformation of CT Hounsfield units (HU) to linear attenuation coefficients at 511 keV (LAC/sub 511/). This cannot be done perfectly from a single peak kilovolt (kVp) CT scan due to variability in Compton and photoelectric composition and, thus, an approximate transformation must be employed. One difficulty in this lies in accurately determining the linear attenuation coefficients (LAC) in actual human tissue. Typically, phantoms consisting of synthetic materials thought to be approximate human tissue equivalents are employed instead. A potentially more accurate approach would be to use dual kVp CT scans to estimate LAC/sub 511/ in actual human tissue and then base the single kVp transformation on these data. This approach would also permit an assessment of the dispersion of actual tissue values about the two-component trend lines typically used for the single kVp transformation. In this paper, we develop and assess this methodology.

CT-based attenuation correction for PET/CT scanners in the presence of contrast agent

In PET/CT tomographs the PET emission data can be corrected for photon attenuation effects using the CT images which are scaled from the mean CT energy of /spl sim/70 keV to the PET photon energy of 511 keV. The standard scaling approach requires segmenting the CT image voxels into soft tissue or bone using a single threshold of 300 H.U. and then applying two separate scale factors. In practice oral contrast may be administered leading to enhanced CT values that are not correctly handled by the standard scaling algorithm, which then leads to a bias in the PET emission image corrected for attenuation. A modified algorithm is proposed which transforms the oral contrast enhanced CT values to the correct 511 keV value, leading to unbiased attenuation correction factors.

Physiologic Changes in a Nonhuman Primate Model of HIV-Associated Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is increased in HIV, but its pathogenesis is not fully understood. Nonhuman primates infected with simian immunodeficiency virus (SIV) or SIV-HIV chimeric virus (SHIV) exhibit histologic changes characteristic of human PAH, but whether hemodynamic changes accompany this pathology is unknown. Repeated measurements of pulmonary artery pressures would permit longitudinal assessments of disease development and provide insights into pathogenesis. We tested the hypothesis that SIV-infected and SHIV-infected macaques develop physiologic manifestations of PAH. We performed right heart catheterizations, echocardiography, and computed tomography (CT) scans in macaques infected with either SIV (ΔB670) or SHIV (89.6P), and compared right heart and pulmonary artery pressures, as well as pulmonary vascular changes on CT scans, with those in uninfected control animals. Right atrial, right ventricular systolic, and pulmonary artery pressures (PAPs) were significantly elevated in 100% of macaques infected with either SIV or SHIV compared with control animals, with no difference in pulmonary capillary wedge pressure. PAPs increased as early as 3 months after SIV infection. Radiographic evidence of pulmonary vascular pruning was also found. Both SIV-infected and SHIV-infected macaques exhibited histologic changes in pulmonary arteries, predominantly consisting of intimal and medial hyperplasia. This report is the first to demonstrate SHIV-infected and SIV-infected macaques develop pulmonary hypertension at a high frequency, with physiologic changes occurring as early as 3 months after infection. These studies establish an important nonhuman primate model of HIV-associated PAH that will be useful in studies of disease pathogenesis and the efficacy of interventions.

PET/CT artifacts

There are several artifacts encountered in positron emission tomography/computed tomographic (PET/CT) imaging, including attenuation correction (AC) artifacts associated with using CT for AC. Several artifacts can mimic a 2-deoxy-2-[18F] fluoro-d-glucose (FDG) avid malignant lesions and therefore recognition of these artifacts is clinically relevant. Our goal was to identify and characterize these artifacts and also discuss some protocol variables that may affect image quality in PET/CT.

Continuous bed motion acquisition on a whole body combined PET/CT system

The continuous motion of the patient bed during the acquisition of PET data represents an alternative to the standard step and shoot protocol where a sequence of discrete, overlapping steps are performed. This PET acquisition mode, similar to the whole body CT scan in which the patient bed moves continuously through the scanner has significant advantages, including uniform axial signal-to-noise ratio (SNR), elimination of resolution artifacts by sampling continuously in the axial direction and a reduction in noise from detector normalization. We have implemented and evaluated continuous bed motion acquisition on the combined PET/CT scanner (CPS Innovations, Knoxville, TN). Methods: Emission data were acquired in list mode format with the bed moving at a constant velocity. The position of the bed was recorded in a separate file together with the current event count. The list mode data were then rebinned into sinograms and reconstructed using the same routines applied to reconstruct the standard images. Each sinogram corresponded to an axial plane thickness of 2.4 mm. Phantom data were acquired with both the standard discrete, overlapping steps and with continuous movement of the bed. Data were collected for a whole body phantom containing lesions carefully positioned in the overlap region between two bed positions to specifically emphasize the effect of the improved SNR. Results: The continuous movement of the patient bed resulted in a uniform axial SNR, improving lesion detectability in the bed overlap region. The continuous axial sampling allowed the 10mm lesion in the whole body phantom to have 45% improvement in contrast compared to the step and shoot acquisition. Patient studies demonstrated improved detectability due to finer axial sampling and uniform SNR.

Human Biodistribution and Dosimetry of the D2/3 Agonist 11C-N-Propylnorapomorphine (11C-NPA) Determined from PET

We measured the whole-body distribution of intravenously injected 11C-N-propylnorapomorphine (11C-NPA), a dopamine agonist PET tracer, in human subjects and determined the resulting absorbed radiation doses. Methods: Six subjects (3 women, 3 men) were injected with 11C-NPA (nominal dose, 370 MBq). A total of 9 consecutive whole-body PET scans were obtained for each subject. In addition, time–activity curves for 12 organs were determined, and residence times were computed for each subject. Dosimetry was determined for the various body organs and the whole body. Results: The average NPA whole-body radiation dose was 3.17 × 10−3 mSv per MBq of injected 11C-NPA. The organ receiving the highest dose was the gallbladder wall, with an average of 2.81 × 10−2 mSv·MBq−1. Conclusion: On the basis of averaged dosimetry results, an administration of less than 1,780 MBq (<48 mCi) of 11C-NPA yields an organ dose of under 50 mSv (5 rem) to all organs.

Continuous bed motion acquisition for an LSO PET/CT scanner

Standard whole-body PET/CT protocols collect PET emission data for a sequence of discrete, overlapping bed positions. An alternative acquisition mode in which the patient bed moves continuously through the scanner has some significant advantages, including uniform axial signal-to-noise, elimination of resolution artifacts by sampling continuously in the axial direction, and a reduction in both noise from detector normalization and artifacts from small patient movements. To validate this approach, continuous bed motion acquisition has been implemented on a high resolution, 16-slice LSO PET/CT scanner (CPS Innovations, Knoxville, TN). The emission data are acquired in list mode with the bed moving at a constant velocity in the range 0.3-0.7 mm/s for a total scan time in patients of around 20 minutes covering an axial extent of 36-84 cm. The absolute position of the bed is read and inserted directly into the list mode data stream. Following acquisition, the emission data are rebinned into a fully 3D data set and reconstructed using a 3D OSEM algorithm. Continuous movement of the patient bed yields uniform signal-to-noise throughout the axial imaging field. For short imaging times, the bed movement in the standard acquisition becomes a significant fraction of the total scan time and continuous bed motion acquisition offers a more efficient alternative. Results are presented for some representative patient studies with both step-and-shoot and continuous bed motion acquisition.