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Biomedical subjects

J M Hoffman

Publications and source records attributed to J M Hoffman.

At least 73 records · Page 4Linked to original sources

Optimum scanning protocol for FDG-PET evaluation of pulmonary malignancy.

UNLABELLED: FDG-PET can differentiate benign from malignant focal pulmonary opacities. We performed dynamic FDG-PET studies to determine the optimum time for emission data acquisition. METHODS: Patients with focal pulmonary abnormalities demonstrated by biopsy to be malignant (n = 10) or benign (n = 4) were evaluated with dynamic FDG-PET. Dynamic PET data were acquired as sequential 5-min images for 2.5 hr. Radioactivity concentration measurements of the focal abnormality, a similar area in the opposite lung, and both lungs in the field of view were made throughout the period of acquisition. Standardized uptake ratios (SUR) of the lesions were calculated. SUR data and lesion-to-background ratios were plotted. The time that the SUR provided the maximum separation between benign and malignant masses after FDG administration was determined. RESULTS: The SUR values provided the greatest separation between benign and malignant abnormalities beginning at 50 min and no advantage was identified in imaging later. Achievement of a 4:1 lesion-to-background ratio occurred by 50 min in malignant lesions. CONCLUSION: The acquisition of the emission data used in the evaluation of pulmonary malignancy should begin approximately 50 min after FDG administration.

Deoxyglucose↗

Neuronal migration disorders: positron emission tomography correlations.

We analyzed the interictal [18F]fluoro-2-deoxy-D-glucose positron emission tomography (PET) findings of 17 epileptic patients with neuronal migration disorders (NMDs). Fifteen patients had abnormal PET findings, i.e., focal hypometabolism in 9 patients and displaced metabolic activity of normal gray matter in 6. All 15 patients had magnetic resonance imaging (MRI) abnormalities; however, PET abnormality assisted in the identification of NMDs on MRI in 3 patients. Two patients with negative MRI also had negative PET studies. PET hypometabolism appeared to correlate with severity of neuronal dysgenesis or temporal lobe involvement, or both. Displaced metabolic activity of gray matter is regarded as a unique interictal [18F]fluoro-2-deoxy-D-glucose-PET finding in NMD. This study demonstrates variable metabolic patterns in NMD and that PET may be a useful complement to MRI in the evaluation of NMD.

Adult↗

Clinical signs and symptoms in pulmonary embolism. A reassessment.

The clinical diagnosis of pulmonary embolism (PE) remains difficult despite years of investigation. The clinical signs and symptoms of pulmonary embolism are numerous, but they are not diagnostically accurate. Radionuclide ventilation perfusion imaging (VQ) has become an important adjunct in screening patients for suspected PE. This study re-evaluates the predictive capabilities of various clinical signs and symptoms in a population of patients in whom angiography was thought to be necessary because of clinical concern for PE. One hundred one patients with suspected PE were retrospectively identified. Clinical information on them was complete, and laboratory studies, VQ imaging, and pulmonary angiography were performed. Thirty-seven clinical signs, symptoms, and other characteristics were individually compared for patients whose angiographic results were positive or negative for PE. Modifying or interactive effects on PE were then examined with logistic regression analysis. Several clinical conditions, including immobilization and recent surgery, were significantly associated with PE. Shortness of breath and history of smoking were significantly associated with negative results on pulmonary angiography. A "high probability" VQ scan was highly predictive (P < .0001) of positive results on angiography. When interactive factors for PE were examined, lack of shortness of breath and arterial pH < or = 7.45, lack of shortness of breath and respiratory rate > 23, diaphoresis in a nonsmoker and immobilized female, were significantly associated with PE. This study again documents the difficulty in using clinical criteria--including signs, symptoms, and laboratory determinations--to predict PE accurately, even in a population in which PE was of clinical concern irrespective of the VQ scan results.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗

Persistent or recurrent bronchogenic carcinoma: detection with PET and 2-[F-18]-2-deoxy-D-glucose.

PURPOSE: To assess positron emission tomography (PET) with 2-[fluorine-18]-2-deoxy-D-glucose (FDG) in the differentiation of recurrent bronchogenic carcinoma from fibrosis after therapy. MATERIALS AND METHODS: Any patient treated for bronchogenic carcinoma who had a residual chest radiographic abnormality was eligible. Forty-three patients (mean age, 63.5 years) participated. Chest radiographs and thoracic computed tomographic scans helped localize the abnormality prior to PET. Semiquantitative analysis was performed on FDG PET images with calculated standardized uptake ratios (SURs). Sensitivity, specificity, and confidence intervals for recurrent disease were determined. RESULTS: Thirty-five patients had recurrent or persistent tumor (median SUR, 7.6; range, 1.9-18.7). Eight patients had fibrosis but no evidence of disease (SUR, 1.6; range, 0.6-2.4). The sensitivity for detecting recurrent tumor (SUR > 2.5) was 97.1%, and specificity was 100%. The SUR for recurrent tumor was statistically significantly higher than for fibrosis (P = .0001). CONCLUSION: FDG PET accurately helps differentiate recurrent bronchogenic carcinoma from fibrosis.

Carcinoma, Bronchogenic↗

Focal cerebral metabolic abnormality in a patient with continuous spike waves during slow-wave sleep.

We report an 11-year-old boy with continuous spike-wave discharges during sleep accompanied by partial motor and atypical absence seizures, psychomotor regression, and severe behavior problems. During wakefulness, epileptiform discharges occurred over the right parietal region, suggesting that the continuous spike-wave discharges during sleep were a manifestation of secondary bilateral synchrony. Bilateral suppression of the spike-and-wave activity was observed after right-sided intracarotid amobarbital injection, further supporting the impression of secondary bilateral synchrony. The right superior temporoparietal increase in metabolic activity during continuous spike-wave discharges and noncontinuous spike-wave discharges was seen on [18F]fluorodeoxyglucose positron emission tomography and supports a right temporoparietal focus in our case. The presence of a focal abnormality suggests that surgical therapy may be effective.

Amobarbital↗

Neuroimaging in infantile autism.

Metabolic findings using [18F]fluorodeoxyglucose (FDG) with positron emission tomography (PET) and correlative anatomic findings with computed tomography (CT) or magnetic resonance imaging (MRI) were characterized in 13 children with infantile autism. Four of 13 patients had both an abnormal FDG-PET and an abnormal MRI, whereas seven of 13 patients had both a normal FDG-PET and a normal CT or MRI. Sixteen of a total of 195 brain areas qualitatively examined with FDG-PET had a hypometabolic abnormality on PET. Three of the five abnormal structural imaging studies revealed neuronal migrational anomalies (focal pachygyria). In two of the five patients with anatomic abnormalities, these were noted only after knowledge of the FDG-PET findings. Our experience reveals that anatomic and metabolic abnormalities can be found in children who exhibit autistic behavior. An FDG-PET study may provide evidence of metabolic dysfunction after an initially unremarkable MRI scan because subtle anatomic abnormalities (as those seen with neuronal migrational anomalies) may be found only after knowledge of a regional metabolic abnormality.

Autistic Disorder↗

Neural correlates of dementia: regional brain metabolism (FDG-PET) and the CERAD neuropsychological battery.

The present Investigation examined the biological correlates of the cognitive deficits of Alzheimer's disease and related dementias using the neuropsychological assessment battery of the Consortium to Establish a Registry of Alzheimer's Disease (CERAD) and positron emission tomography (PET). Resting state cerebral glucose metabolism was measured using the labelled radiotracer, [18F] Fluoro-2-deoxyglucose (FDG), in a sample of patients with mild to moderate dementia (n = 66). Specific and predictable relationships were seen between regional brain metabolism (left and right, frontal, temporal, and parietal lobes) and the neuropsychological measures of verbal fluency, constructional praxis, and verbal list learning. On tests of naming and delayed verbal recall only diminished FDG uptake in the left frontal lobe and the left temporal lobe, respectively, approached significance. This study demonstrates the expected relationships between neuropsychological performance and regional cerebral metabolism, thereby providing support for the CERAD battery as a valid measure in the clinical evaluation of dementia and for the use of FDG-PET in brain-behavior studies of dementia.

Journal Article↗

Semiquantitative and visual analysis of FDG-PET images in pulmonary abnormalities.

UNLABELLED: FDG PET images of the thorax can be analyzed semiquantitatively using standardized uptake ratios (SUR) or activity ratios between abnormal and normal tissue, or qualitatively by visual comparison of the abnormality to normal structures. Standardized uptake ratio evaluation of FDG PET images has been shown to accurately differentiate benign from malignant focal pulmonary abnormalities. The accuracy of activity ratios and visual analysis have not been evaluated. We therefore prospectively analyzed FDG PET images in patients with pulmonary abnormalities to evaluate differences in analytic schemes. METHODS: We evaluated 107 patients with an indeterminate focal abnormality on chest radiograph or CT with FDG PET between November 1991 and March 1993. The PET studies were evaluated using SUR, activity ratios and visual analysis. Activity ratios of maximum activity/cc and average activity/cc between regions of interest (ROIs) in abnormalities and normal lung on the contralateral side were calculated. Visual interpretations were graded on a five-point scale of two observers' confidence of malignancy. FDG uptake in the abnormality was also visually graded in comparison to mediastinal activity. Receiver-operating characteristic (ROC) curve areas were generated for the SUR data, activity ratios and visual analysis. RESULTS: Of 88 patients in which a conclusive diagnosis was made, 61 (69%) patients had malignancy and 27 (31%) patients had a benign process. SUR, maximum activity ratio, average activity ratio and visual interpretation ROC curve areas were 0.96, 0.95, 0.92 and 0.96, respectively. CONCLUSIONS: SUR, activity ratios and visual evaluation are each equally accurate methods of FDG PET data analysis in differentiating malignant from benign focal pulmonary abnormalities.

Deoxyglucose↗

MR and positron emission tomography in the diagnosis of surgically correctable temporal lobe epilepsy.

PURPOSE: To determine the association of an MR abnormality and a positron emission tomography (PET) abnormality with a good outcome in patients with temporal lobe epilepsy after lobectomy, the association of combined PET and MR findings with good outcomes after lobectomy, and MR and PET pathologic correlation. METHODS: MR and PET were performed on 27 patients in a blinded study. Histologic studies were correlated with foci of increased T2 signal. RESULTS: Increased signal or decreased volume of the hippocampus was noted in 13 of 15 patients with mesial temporal sclerosis. Twelve of 15 had positive PET findings. MR identified 20 (83%) of the 24 patients with good outcomes. PET identified 71%. When MR and PET were combined, they detected 95% of the patients with good outcome. Region of interest measurements of the hippocampus in 11 study patients and 7 control subjects documented a significant increase in signal in the patients with seizures. Histologic correlative studies demonstrated that increased T2 signals related to astrocytosis in the hippocampus and adjacent white matter. CONCLUSIONS: MR (increased signal and decreased volume of the hippocampus) significantly improved the capability to identify those persons who would be helped by lobectomy. MR sensitivity exceeded that of PET.

Adolescent↗

Performance characteristics of a whole-body PET scanner.

METHODS: This study characterizes the performance of a newly developed whole-body PET scanner (Advance, General Electric Medical Systems, Milwaukee, WI). The scanner consists of 12,096 bismuth germinate crystals (4.0 mm transaxial by 8.1 mm axial by 30 mm radial) in 18 rings, giving 35 two-dimensional image planes through an axial field of view of 15.2 cm. The rings are separated by retractable tungsten septa. Intrinsic spatial resolution, scatter fraction, sensitivity, high count rate performance and image quality are evaluated. RESULTS: Transaxial resolution (in FWHM) is 3.8 mm at the center and increases to 5.0 mm tangential and 7.3 mm radial at R = 20 cm. Average axial resolution decreases from 4.0 mm FWHM at the center to 6.6 mm at R = 20 cm. Scatter fraction is 9.4% and 10.2% for direct and cross slices, respectively. With septa out, the average scatter fraction is 34%. Total system sensitivity for true events (in kcps/(microCi/cc)) is 223 with septa in and 1200 with septa out. Dead-time losses of 50% correspond to a radioactivity concentration of 4.9 (0.81) microCi/cc and a true event count rate of 489 (480) kcps with septa in (out). Noise-equivalent count rate (NECR) for the system as a whole shows a maximum of 261 (159) kcps at a radioactivity concentration of 4.1 (0.65) microCi/cc with septa in (out). NECR is insensitive to changes in lower gamma-energy discrimination between 250-350 keV. CONCLUSIONS: The results show the performance of the newly designed PET scanner to be well suited for clinical and research applications.

Brain↗

Cerebral imaging of decompression injury patients with 18-F-2-fluoro-2-deoxyglucose positron emission tomography.

The objective assessment of the extent of cerebral insult and the effects of therapy in decompression injury patients has proven to be difficult by most imaging modalities. In this pilot study we evaluated the ability of 18-F-2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) to identify metabolic brain abnormalities in decompression injury patients. Twenty-two patients who were evaluated at our institution for decompression accidents were evaluated with FDG-PET. Four of the 22 patients had no neurologic symptoms and no neurologic findings on clinical exam at the time of the FDG-PET study. No statistically significant correlations were found between the presence of symptoms and the demonstration of abnormalities on the PET study and no statistically significant correlation was found between the location of the decompression injury and the demonstration of abnormalities on the PET study. We conclude that FDG-PET imaging of the brain cannot reliably identify cerebral abnormalities in patients with decompression injuries and would be of limited benefit for monitoring therapy in patients with decompression illness.

Adult↗

Synthesis and evaluation of 2-pyridinone derivatives as HIV-1-specific reverse transcriptase inhibitors. 4. 3-[2-(Benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one and analogues.

A new series of potent specific 2-pyridinone reverse transcriptase (RT) inhibitors was developed based on the preliminary development lead 3-[(phthalmido)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one (3), a non-nucleoside derivative which exhibited weak antiviral activity in cell culture against HIV-1 strain IIIB. One compound, 3-[(benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one (9,L-696,229), which was a highly selective antagonist of the RT enzyme (IC50 = 23 nM) and which inhibited the spread of HIV-1 IIIB infection by > 95% in MT4 human T-lymphoid cell culture (CIC95 = 50-100 nM), was selected for clinical evaluation as an antiviral agent.

Antiviral Agents↗

Synthesis and evaluation of 2-pyridinone derivatives as specific HIV-1 reverse transcriptase inhibitors. 3. Pyridyl and phenyl analogs of 3-aminopyridin-2(1H)-one.

In an ongoing effort to develop novel nonnucleoside, specific human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitors, a series of 3-[(pyridylmethyl)amino]- and 3-[(phenylmethyl)amino]-2-pyridinone derivatives was synthesized and tested for HIV-1 RT inhibitory activity. The more potent compounds have a 2'-methoxy group and 4'- and/or 5'-aliphatic substituents on the pyridyl and phenyl rings. Several of the more potent compounds were also evaluated for antiviral activity in MT-4 cell culture. From this series of compounds, 3-[N-[(5-ethyl-2-methoxy-6-methyl-3-pyridyl)methyl]amino]-5-ethyl-6- methylpyridin-2(1H)-one (6) was selected for clinical evaluation.

Aminopyridines↗

Comparison of serial PET and MRI scans in a pediatric patient with a brainstem glioma.

Profound clinical deficits may be associated with insults to the brainstem, making management of patients with brainstem gliomas very complex. Small changes in the radiographic appearance of a brainstem tumor may be associated with significant clinical deterioration. Furthermore, both magnetic resonance imaging and computed tomography are frequently unable to differentiate between therapy-related tissue reactions and progressive tumor. Two clinical scenarios particularly difficult to resolve include: (1) transient radiographic and clinical deterioration following hyperfractionated radiotherapy, and (2) clinical deterioration in a patient who has failed initial therapy, but has stable radiographic findings following a second therapy. We report a child with a pontine glioma whose tumor progression was demonstrated more convincingly with a 18F-deoxyglucose positron emission scan than with magnetic resonance imaging. PET scans may be helpful in confirming that tumor progression is responsible for clinical deterioration in a patient whose MRI scans remain stable.

Brain Neoplasms↗