Thomas C. Hawk

Brain morphological changes and early marijuana use: a magnetic resonance and positron emission tomography study.

Abstract Background: The focus of this report is on the possible role that the age of first use of marijuana may play on brain morphology and function. Methods: Magnetic resonance imaging (MRI) and positron emission tomography (PET) were utilized to study 57 subjects. Brain volume measures (whole brain, gray matter, white matter and lateral ventricle volumes), global cerebral blood flow (CBF) and body size were evaluated. Results: There are three primary findings related to age of first use of marijuana. Subjects who started using marijuana before age 17, compared to those who started later, had smaller whole brain and percent cortical gray matter and larger percent white matter volumes. Functionally, males who started using marijuana before 17 had significantly higher CBF than other males. Both males and females who started younger were physically smaller in height and weight, with the effects being greater in males. Conclusions: These findings suggest that the age at which exposure to marijuana begins is important. Early adolescence may be a critical period for effects that are not present when exposure begins later. These results are discussed in light of reported effects of marijuana on gonadal and pituitary hormones.

Time course of tetrahydrocannabinol-induced changes in regional cerebral blood flow measured with positron emission tomography

While several studies are available on the immediate effects of marijuana and its active ingredient tetrahydrocannabinol (THC) on regional cerebral blood flow (rCBF), we examined the effects of intravenous infusion of THC on rCBF and behavior over a 120-min. period using positron emission tomography. Indices of rCBF, intoxication and physiology were measured at baseline and 30, 60, 90 and 120 min. after a 20-min. intravenous infusion of 0.15 or 0.25 mg/min. of THC, or placebo given to 47 subjects. The rCBF remained increased up to 120 min. after the high-dose THC infusion. Significant increases were seen in global perfusion and in the frontal, insular and anterior cingulate regions. Changes were greater in the right hemisphere. After the high dose, cerebellar flow was increased at both 30 and 60 min. The anterioposterior ratio of cortical rCBF increased in both hemispheres, and remained significantly greater than in the placebo condition until 120 min. in the right hemisphere. Intoxication peaked at 30 min. and remained elevated at 120 min. THC had significant effects on global CBF and rCBF, and feeling intoxicated accounted for changes in rCBF better than plasma level of THC.

Regional Brain Activation in Response to Rectal Distension in Patients with Irritable Bowel Syndrome and the Effect of a History of Abuse

Previous studies have demonstrated alterations in brain response to rectal distension in patients with irritable bowel syndrome (IBS) compared to controls. Our aim was to compare regional brain activity in response to rectal balloon distension in patients with IBS and healthy controls. We studied six patients with IBS and six healthy controls. Positron emission tomography scans were obtained during rectal balloon distensions. Statistical parametric mapping and region of interest analysis were performed to identify and compare differences in regional cerebral blood flow (CBF) for each distension pressure within and between the groups of interest. In post-hoc analyses, patients with a history of sexual or physical abuse were compared to patients without abuse. In response to rectal distension, controls exhibit a greater increase in anterior cingulate cortex (ACC) activity compared to the IBS group (Z = 3.2, P = 0.001). Thalamic activity was higher in the IBS patients relative to the control group (Z = 3.3, P < 0.001). Increased ACC activity was observed in IBS patients with no history of abuse (Z = 5.2, P < 0.001) similar to controls, whereas no such increased activity was noticed in the abused group. In conclusion, this study replicates previous findings showing alterations in brain response to rectal distension in patients with IBS. The observations on the effect of abuse suggest a possible modulating role of abuse history on this brain response.

Regional Brain Activity Correlates of Nicotine Dependence

Fifteen smokers participated in a study investigating brain correlates of nicotine dependence. Dependence was reduced by having subjects switch to denicotinized cigarettes for 2 weeks while wearing nicotine skin patches. Positron emission tomography (PET) scans assessed regional cerebral metabolic rate for glucose (rCMRglc) after overnight nicotine abstinence on three occasions: (1) at baseline; (2) after 2 weeks of exposure to denicotinized cigarettes+nicotine patches; and (3) 2 weeks after returning to smoking the usual brands of cigarettes. Craving for cigarettes and scores on the Fagerström Test of Nicotine Dependence (FTND) questionnaire decreased at the second session relative to the first and last sessions. Regional brain metabolic activity (normalized to whole brain values) at session 2 also showed a significant decrease in the right hemisphere anterior cingulate cortex. Exploratory post hoc analyses showed that the change in craving across sessions was negatively correlated with the change in rCMRglc in several structures within the brain reward system, including the ventral striatum, orbitofrontal cortex and pons. The between-session difference in thalamus activity (right hemisphere) was positively correlated with the difference in FTND scores. Correlational analyses also revealed that reported smoking for calming effects was associated with a decrease (at session 2) in thalamus activity (bilaterally) and with an increase in amygdala activity (left hemisphere). Reported smoking to enhance pleasurable relaxation was associated with an increase in metabolic activity of the dorsal striatum (caudate, putamen) at session 2. These findings suggest that reversible changes in regional brain metabolic activity occur in conjunction with alterations in nicotine dependence. The results also highlight the likely role of thalamic gating processes as well as striatal reward and corticolimbic regulatory pathways in the maintenance of cigarette addiction.

Aging and Attentional Guidance During Visual Search: Functional Neuroanatomy by Positron Emission Tomography

Positron emission tomography (PET) was used to examine adult age differences in neural activation during visual search. Target detection was less accurate for older adults than for younger adults, but both age groups were successful in using color to guide attention to a subset of display items. Increasing perceptual difficulty led to greater activation of occipitotemporal cortex for younger adults than for older adults, apparently as the result of older adults maintaining higher levels of activation within the easier task conditions. The results suggest that compensation for age-related decline in the efficiency of occipitotemporal cortical functioning was implemented by changes in the relative level of activation within this visual processing pathway, rather than by the recruitment of other cortical regions.

PET of hypoxia and perfusion with 62Cu-ATSM and 62Cu-PTSM using a 62Zn/62Cu generator.

OBJECTIVE Copper-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) and copper-pyruvaldehyde-bis(N4-methylthiosemicarbazone) (Cu-PTSM) are being studied as potential markers of hypoxia and perfusion, respectively. The use of short-lived radionuclides (e.g., 62Cu) has advantages for clinical PET, including a lower radiation dose than long-lived radionuclides and serial imaging capability. A 62Zn/62Cu microgenerator and rapid synthesis kits now provide a practical means of producing 62Cu-PTSM and 62Cu-ATSM on-site. Tumors can be characterized with 62Cu-PTSM, 62Cu-ATSM, and 18F-FDG PET scans during one session. We present the initial clinical data in two patients with lung neoplasms. CONCLUSION Hypoxia and perfusion are important parameters in tumor physiology and can have major implications in diagnosis, prognosis, treatment planning, and response to therapy. We have shown the feasibility of performing 62Cu-ATSM and 62Cu-PTSM PET together with FDG PET/CT during a single imaging session to provide information on both perfusion and hypoxia and tumor anatomy and metabolism.

PET and brain tumor image fusion.

PET imaging with (18)F-2-deoxy-2-fluoro-D-glucose (FDG-PET) is useful both for the initial evaluation of brain tumors and for follow up after therapy. Over 400 FDG-PET studies are performed at Duke University Medical Center annually for brain tumors. Image registration of FDG-PET data with anatomic imaging (MRI) is essential to accurately localize the abnormality in the brain because of the metabolic heterogeneity of brain tumors and the high background metabolism of normal cerebral cortex. A practical semi-automated image registration technique has been developed which is used routinely for all brain tumor patients. In the future, image registration will likely become increasingly important for FDG and other PET tracers used for brain tumor imaging, and the combined functional/anatomic information will be utilized directly for therapeutic radiation and surgical treatment planning.

PET prostate imaging with small planar detectors

PET imaging in the pelvis with dual planar detectors has been investigated. The scanner consisted of two 20 cm (transaxial)times15 cm (axial) planar detectors with 3times3times10 mm3 LGSO elements mounted on a rotating gantry with adjustable detector radii. A 36 cmtimes21 cm oval phantom, 40 cm long, with a centered 2.2 cm sphere and 1.3 cm neighboring spheres was used for tests with the spheres at 20:1, 10:1, and 5:1 concentrations relative to the background. Data were acquired with the detectors in a fixed anterior-posterior orientation as well as orbiting the body in limited and full arcs. Images were reconstructed with a fully 3D ML-EM algorithm (in most cases with limited angles.) For the fixed detector position, coronal views showed the larger sphere and the lateral small sphere for the 20:1 and 10:1 concentrations. Transaxial images showed many artifacts in the limited-angle cases. For the orbiting detector data, transaxial image quality improved as the number of angles increased. Significant artifacts were still present, however. The system works satisfactorily, even with limited views, for detection of high-uptake lesions. Further characterization of uptake requires fuller angular sampling

FDG-PET Assessment of the Effect of Head and Neck Radiotherapy on Parotid Gland Glucose Metabolism

PURPOSE Functional imaging with [F-18]-fluorodeoxyglucose positron emission tomography (FDG-PET) provides the opportunity to define the physiology of the major salivary glands before and after radiation therapy. The goal of this retrospective study was to identify the radiation dose-response relationship of parotid gland glucose metabolism in patients with head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS Forty-nine adults with HNSCC were identified who had curative intent intensity-modulated radiation therapy (IMRT) and FDG-PET imaging before and after treatment. Using a graphical user interface, contours were delineated for the parotid glands on axial CT slices while all authors were blinded to paired PET slices. Average and maximal standard uptake values (SUV) were measured within these anatomic regions. Changes in SUV and volume after radiation therapy were correlated with parotid gland dose-volume histograms from IMRT plans. RESULTS The average parotid gland volume was 30.7 mL and contracted 3.9 ± 1.9% with every increase of 10 Gy in mean dose (p = 0.04). However, within the first 3 months after treatment, there was a uniform reduction of 16.5% ± 7.3% regardless of dose. The average SUV(mean) of the glands was 1.63 ± 0.48 pretreatment and declined by 5.2% ± 2.5% for every increase of 10 Gy in mean dose (p = 0.04). The average SUV(max) was 4.07 ± 2.85 pretreatment and decreased in a sigmoid manner with mean dose. A threshold of 32 Gy for mean dose existed, after which SUV(max) declined rapidly. CONCLUSION Radiation dose responses of the parotid glands can be measured by integrated CT/FDG-PET scans. Retrospective analysis showed sigmoidal declines in the maximum metabolism but linear declines in the average metabolism of the glands with dose. Future studies should correlate this decline in FDG uptake with saliva production to improve treatment planning.

Detection of Recurrent Brain Tumor: Comparison of MR Registered Camera-Based and Dedicated PET Images

The purpose of this study is to compare the quality of images and the results of camera-based and dedicated position emission tomography (PET) in the same patients with suspected recurrent or persistent brain tumor after therapy. Both PET studies were interpreted using registration with contrast-enhanced magnetic resonance imaging (MRI) studies. Twenty-three patients with 24 contrast-enhancing lesions by MRI were included. Camera-based PET images were more difficult to register and resulted in less accurate automated determination of the edge because of image noise. Dedicated PET images demonstrated better gray matter to white matter discrimination in every patient. Camera-based PET identified tumor in 17 of 19 lesions that were abnormal for tumor by dedicated PET. Camera-based PET identified absence of tumor in 4 of 5 lesions considered negative for tumor by dedicated PET. Thus, despite the limitations related to camera-based PET, the overall concordance of interpretation using MRI registered images is good.