Radiologic Responses in Cynomolgus Macaques for Assessing Tuberculosis Chemotherapy Regimens.

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.

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.

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 (18)F-fluorodeoxyglucose ((18)FDG) 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.

PET/CT today and tomorrow.

UNLABELLED: Accurate anatomic localization of functional abnormalities seen with PET is known to be problematic. Even though nonspecific tracers such as 18F-FDG visualize certain normal anatomic structures, the spatial resolution is generally inadequate for localization of pathology. Combining PET with a high-resolution anatomic imaging modality such as CT can resolve the localization issue, as long as the images from the two modalities are accurately coregistered. However, software-based registration techniques have difficulty accounting for differences in patient positioning and involuntary movement of internal organs, often necessitating labor-intensive nonlinear mapping that may not converge to a satisfactory result. Acquiring both CT and PET images in the same scanner obviates the need for software registration and routinely provides accurately aligned images of anatomy and function in a single scan. DISCUSSION: A CT scanner positioned in tandem with a PET scanner and with a common patient couch and operating console has recently been explored as a solution to anatomic and functional image registration. Axial translation of the couch between the two modalities enables both CT and PET data to be acquired during a single imaging session. In addition, the CT images can be used to generate noiseless attenuation correction factors for the PET emission data. By minimizing patient movement between the CT and PET scans, and after accounting for the axial separation of the two modalities, accurately registered anatomic and functional images can be obtained. Since the introduction of the first PET/CT prototype a little over 5 years ago, several thousand cancer patients have been scanned on combined PET/CT devices. In the past 3 years, a number of commercial designs have become available featuring multidetector spiral CT scanners and high-performance PET devices. Initial experience has demonstrated an increased level of accuracy and confidence in the interpretation of the combined study compared with separate readings, particularly in the ability to distinguish pathology from normal physiologic uptake and to precisely localize abnormal foci. CONCLUSION: Combined PET/CT scanners represent an important evolution in technology that is helping to bring molecular imaging to the forefront in cancer diagnosis, staging, and therapy monitoring.