Imaging amyloid deposition in Lewy body diseases.

BACKGROUND: Extrapyramidal motor symptoms precede dementia in Parkinson disease (PDD) by many years, whereas dementia occurs early in dementia with Lewy bodies (DLB). Despite this clinical distinction, the neuropsychological and neuropathologic features of these conditions overlap. In addition to widespread distribution of Lewy bodies, both diseases have variable burdens of neuritic plaques and neurofibrillary tangles characteristic of Alzheimer disease (AD). OBJECTIVES: To determine whether amyloid deposition, as assessed by PET imaging with the beta-amyloid-binding compound Pittsburgh Compound B (PiB), can distinguish DLB from PDD, and to assess whether regional patterns of amyloid deposition correlate with specific motor or cognitive features. METHODS: Eight DLB, 7 PDD, 11 Parkinson disease (PD), 15 AD, and 37 normal control (NC) subjects underwent PiB-PET imaging and neuropsychological assessment. Amyloid burden was quantified using the PiB distribution volume ratio. RESULTS: Cortical amyloid burden was higher in the DLB group than in the PDD group, comparable to the AD group. Amyloid deposition in the PDD group was low, comparable to the PD and NC groups. Relative to global cortical retention, occipital PiB retention was lower in the AD group than in the other groups. For the DLB, PDD, and PD groups, amyloid deposition in the parietal (lateral and precuneus)/posterior cingulate region was related to visuospatial impairment. Striatal PiB retention in the DLB and PDD groups was associated with less impaired motor function. CONCLUSIONS: Global cortical amyloid burden is high in dementia with Lewy bodies (DLB) but low in Parkinson disease dementia. These data suggest that beta-amyloid may contribute selectively to the cognitive impairment of DLB and may contribute to the timing of dementia relative to the motor signs of parkinsonism.

Detection of inflamed atherosclerotic lesions with diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A) and positron-emission tomography.

Diadenosine-5',5'''-P(1),P(4)-tetraphosphate (Ap(4)A) and its analog P(2),P(3)-monochloromethylene diadenosine-5',5'''-P(1),P(4)-tetraphosphate (AppCHClppA) are competitive inhibitors of adenosine diphosphate-induced platelet aggregation, which plays a central role in arterial thrombosis and plaque formation. In this study, we evaluate the imaging capabilities of positron-emission tomography (PET) with P(2),P(3)-[(18)F]monofluoromethylene diadenosine-5',5'''-P(1),P(4)-tetraphosphate ([(18)F]AppCHFppA) to detect atherosclerotic lesions in male New Zealand White rabbits. Three to six months after balloon injury to the aorta, the rabbits were injected with [(18)F]AppCHFppA, and microPET imaging showed rapid accumulation of this radiopharmaceutical in the atherosclerotic abdominal aorta, with lesions clearly visible 30 min after injection. Computed tomographic images were coregistered with PET images to improve delineation of aortoiliac tracer activity. Plaque macrophage density, quantified by immunostaining with RAM11 against rabbit macrophages, correlated with PET measurements of [(18)F]AppCHFppA uptake (r = 0.87, P < 0.0001), whereas smooth-muscle cell density, quantified by immunostaining with 1A4 against smooth muscle actin, did not. Biodistribution studies of [(18)F]AppCHFppA in normal rats indicated typical adenosine dinucleotide behavior with insignificant myocardial uptake and fast kidney clearance. The accumulation of [(18)F]AppCHFppA in macrophage-rich atherosclerotic plaques can be quantified noninvasively with PET. Hence, [(18)F]AppCHFppA holds promise for the noninvasive characterization of vascular inflammation.

Synthesis and evaluation of a new series of 17alpha-[(123)I]iodovinyl estradiols.

A series of 17alpha-substituted estradiols was synthesized in which the stereochemical characteristics of carbons 20 and 21 were modified. It was found that the (Z)-isomer demonstrated more favorable receptor binding affinity than the corresponding (E)-isomer.

Butanol is superior to water for performing positron emission tomography activation studies.

[15(O)]Butanol has been shown to be superior to [15(O)]water for measuring cerebral blood flow with positron emission tomography. This work demonstrates that it is also superior for performing activation studies. Data were collected under three conditions: a visual confrontation animal-naming task, nonsense figure size discrimination, and a nonvisual darkroom control task. Time-activity curves (TAC) were obtained for regions known to be activated by the confrontation naming task to compare absolute uptake and the different kinetics of the two tracers. Also, t statistic maps were calculated from the data of 10 subjects for both tracers and compared for magnitude of change and size of activated regions. Peak uptake in the whole-brain TAC were similar for the two tracers. For all regions and conditions, the washout rate of [15(O)]butanol was 41% greater than that of [15(O)]water. At a threshold of 0, the [15(O)]water and [15(O)]butanol percent difference (nonnormalized) and t statistic (global normalization) images are nearly identical, indicating that the same property is being measured with both tracers. The [15(O)]butanol parametric images displayed at a threshold of /t/ = 5 look similar to the [15(O)]water parametric maps displayed at a threshold of /t/ = 4, which is consistent with the observation that t statistic values in [15(O)]butanol images are generally greater. The t statistic values were equal when the [15(O)]butanol parametric map was created from any subset of 6 subjects and the [15(O)]water parametric map was created from all 10 subjects. Fewer subjects need to be studied with [15(O)]butanol to reach the same statistical power as an [15(O)]water-based study.

Synthesis and evaluation of [18F]1-amino-3-fluorocyclobutane-1-carboxylic acid to image brain tumors.

UNLABELLED: We have developed a new tumor-avid amino acid, 1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC), labeled with 18F for nuclear medicine imaging. METHODS: [18F]FACBC was prepared with high specific activity (no carrier added [NCA]) and was evaluated for its potential in tumor localization. A comparative study was performed for [18F]FACBC and [18F]2-fluorodeoxyglucose (FDG) in which the uptake of each agent in 9L gliosarcoma (implanted intracerebrally in Fisher 344 rats) was measured. In addition, the first human PET study of [18F]FACBC was performed on a patient with residual glioblastoma multiforme. Quantitative brain images of the patient were obtained by using a Siemens 921 47-slice PET imaging system. RESULTS: In the rat brain, the initial level of radioactivity accumulation after injection of [18F]FACBC was low (0.11 percentage injected dose per gram [%ID/g]) at 5 min and increased slightly to 0.26 %ID/g at 60 min. The tumor uptake exhibited a maximum at 60 min (1.72 %ID/g), resulting in a tumor-to-brain ratio increase of 5.58 at 5 min to 6.61 at 60 min. In the patient, the uptake of [18F]FACBC in the tumor exhibited a maximum concentration of 146 nCi/mL at 35 min after injection. The uptake of radioactivity in the normal brain tissue was low, 21 nCi/mL at 15 min after injection, and gradually increased to 29 nCi/mL at 60 min after injection. The ratio of tumor to normal tissue was 6 at 20 min after injection. The [18F]FACBC PET scan showed intense uptake in the left frontal region of the brain. CONCLUSION: The amino acid FACBC can be radiofluorinated for clinical use. [18F]FACBC is a potential PET tracer for tumor imaging.

Polymer-encapsulated PC-12 cells demonstrate high-affinity uptake of dopamine in vitro and 18F-Dopa uptake and metabolism after intracerebral implantation in nonhuman primates.

Intracranial implantation of polymer-encapsulated PC-12 cells has been shown to improve motor behavioral performance in animal models of Parkinson's disease. The purpose of this blinded study was to examine whether such improvement is associated with the active uptake and metabolism of dopamine precursors by intracerebrally implanted polymer-encapsulated PC-12 cells. In an in vitro experiment we demonstrate that 3H-dopamine uptake by PC-12 cells was 10(8) fmol/min x 10(6) cells, and that this uptake can be specifically blocked 88% by the addition of 10nM of nomifensine. In the in vivo experiments, polymer-encapsulated PC-12 cells were implanted in four MPTP-treated monkeys into the left deep parietal white matter (R1) or left striatum (R2-4). A fifth MPTP-treated monkey (R5) served as a control and received left striatal implants of empty capsules. 18-F-Dopa Positron Emission Tomography (PET) imaging was performed on each monkey before and after implantation surgery by blinded investigators. PET images obtained 5-13 wk after implantation demonstrated well delineated focal areas of high 18F-dopa uptake in R1, R2, and R4. The focal area of high 18F-dopa uptake in R1 precisely coregistered on a brain magnetic resonance image to the site of implantation. R3 (in whom the polymer-encapsulated PC-12 cells demonstrated poor cell survival upon explantation) and R5 (empty capsules) failed to demonstrate any area of increased 18F-dopa uptake in their PET images. Histological examination of the host brain revealed no sprouting of dopaminergic nerve terminals around the implantation sites of the polymer-encapsulated PC-12 cells. These results indicate that the previously noted behavioral improvement after intrastriatal implantation of polymer encapsulated PC-12 cells is at least in part due to their highly specific uptake and metabolism of dopamine precursors. Furthermore, these data suggest that polymer-encapsulated PC-12 cells can store, reuptake, and functionally replenish dopamine and therefore, may be an effective treatment for Parkinson's disease.

Fluorine-18-FPCT: a PET radiotracer for imaging dopamine transporters.

UNLABELLED: Fluorine-18-labeled 2 beta-carbomethoxy-3 beta-(4-chlorophenyl)-8-[-3-fluoropropyl) nortropane (FPCT) has been synthesized as a new dopamine transporter imaging agent. METHODS: Fluorine-18 was introduced into 2 beta-carbomethoxy-3 beta-(4-chlorophenyl)-8-[-3-fluoropropyl) nortropane by preparation of 1-[18F]fluoro-3-iodopropane followed by alkylation of 2 beta-carbomethoxy-3 beta-(4-chlorophenyl)nortropane. RESULTS: Tissue distribution studies in rats with [18F]FPCT showed high striatal uptake (0.70% dose/g at 60 min; 0.38% dose/g at 120 min) and good striatal-to-cerebellum ratios (5.5 at 60 min; 6.2 at 120 min). Imaging studies in rhesus monkeys (n = 2) with [18F]FPCT showed high uptake and retention in the putamen (P) (P = 0.03%-0.12% dose/g; at 115 min) and good putamen-to-cerebellum ratios of 3.40-3.43 at 115 min. Plasma metabolites were analyzed in rhesus monkeys (n = 2) by ether extraction and HPLC. The radioactivity in the ether-extractable fraction displayed a single peak that corresponded on HPLC to unmetabolized authentic FPCT. CONCLUSION: These results suggest that [18F]FPCT is an excellent candidate for PET imaging of dopamine transporters.

Positron emission tomographic analysis of central 5-hydroxytryptamine2 receptor occupancy in healthy volunteers treated with the novel antipsychotic agent, ziprasidone.

Ziprasidone is a novel antipsychotic agent, with high affinity for dopamine D2 and serotonin (5-HT2) receptors in vitro and in animal models. The goal of this study was to determine the time course of 5-HT2 receptor occupancy (%RO) in healthy humans after a single p.o. dose. Positron emission tomography with the 5-HT2 ligand, [18F]setoperone, was performed in eight male volunteers, in the drug-naive, base-line (BL) state and 4 to 18 hr after ziprasidone (40 mg). Cerebral cortical binding potential [BP, maximum number of available receptors/KD or association rate for specific binding (k3)/dissociation rate for specific binding (k4)] was estimated using the cerebellum as reference. Transport rate from plasma to brain (K1), transport rate from brain to plasma (k2), association rate of nonspecific binding (k5) and dissociation rate of nonspecific binding (k6) were derived by fitting cerebellar time-activity curves to a three-compartment model. Fitting of cortical data to a 4-compartment model with K1/k2, k5 and k6, fixed at cerebellar values, was used to determine k3 and k4. %RO was calculated using the relation: %RO = [(BPBL-BPDRUG)/BPBL] x 100%. At BL, cortical parameter (mean +/- S.E.M) were: K1 = 0.121 +/- 0.0072 ml.min-1.g-1; k2 = 0.0581 +/- 0.004 min-1; k3 = 0.321 +/- 0.0026 min-1; k4 = 0.0957 +/- 0.0059 min-1; k5 = 0.0147 +/- 0.00066 min-1; and k6 = 0.0059 +/- 0.00042 min-1. Ziprasidone did not effect K1, k2, k5 or k6; however, k3 was reduced and k4 was elevated (P < .01). RO was nearly complete at 4 hr after dosing (98%) and remained elevated at 18 hr (46%). Plasma concentrations were well described by a biexponential function and decreased much more rapidly than RO. These results establish that ziprasidone has high potency for blocking 5-HT2 receptors in healthy humans; a potentially important characteristic of atypical antipsychotic agents.

Cocaine congeners as PET imaging probes for dopamine terminals.

UNLABELLED: The PET imaging properties of three phenyltropane drugs with differing affinities and selectivities for the dopamine over serotonin transporter, were compared. METHODS: Carbon-11-CFT (WIN 35,428, 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane), 11C-CCT (RTI-131, 2 beta-carbomethoxy-3 beta-(4-monochlorophenyl)tropane), and 11C-CDCT (dichloropane, 2 beta-carbomethoxy-3 beta-(3,4-dichlorophenyl)tropane) were evaluated as imaging probes for dopamine neurons in five normal and in two MPTP-treated cynomolgus monkeys (macaca fascicularis) using a high-resolution PET imaging system (PCR-I). RESULTS: For 11C-CFT, the specific binding ratio (as defined by the ratio of radioactivity levels in striatum versus cerebellum) was 4.2 +/- 0.8 in caudate and 4.9 +/- 1.2 in putamen at 60 min and 4.9 +/- 1.2 and 5.5 +/- 1.1 at 90 min in control animals. In MPTP-treated monkeys the corresponding ratios were 1.4 +/- 0.1 in caudate and 1.5 +/- 0.1 in putamen at 60 min and 1.3 +/- 0.1 in caudate and 1.4 +/- 0.3 in putamen at 90 min. For the monochloro analog of CFT, 11C-CCT, the ratios in control caudate and putamen were 2.7 +/- 0.4 and 3.4 +/- 0.3, respectively, at 60 min and 3.7 +/- 0.5 and 4.4 +/- 0.6, respectively, at 90 min. In MPTP-treated animals, corresponding ratios were 1.4 +/- 0.4 and 1.5 +/- 0.3 at 60 min and 1.4 +/- 0.4 and 1.6 +/- 0.4 at 90 min. The dichloro analog of CFT, CDCT, which has the highest affinity for the dopamine transporter, generated the lowest ratios in control brains, 2.3 +/- 0.4 in caudate and 2.4 +/- 0.5 in putamen at 60 min. In one MPTP-treated monkey, the corresponding ratios were 1.6 +/- 0.4 and 1.8 +/- 0.3. In comparison with 11C-CFT, both 11C-CCT and 11C-CDCT were less selective and had high uptake in the thalamus. CONCLUSION: The present results clearly indicate that 11C-CFT is a useful ligand for monitoring dopamine neuronal degeneration.

Preparation and biological evaluation of iodine-125-IACFT: a selective SPECT agent for imaging dopamine transporter sites.

UNLABELLED: Parkinson's disease is a progressive neurodegenerative disorder that is associated with the loss of nerve terminals from specific brain areas, particularly in the caudate and putamen, which contains the highest concentrations of dopamine transporter sites. Previously, we synthesized and evaluated a series of 11C-labeled 2 beta-carbomethoxy -3 beta-aryltropane (WIN 35,428; CFT) derivatives as markers for the dopamine transporter system. These ligands have high affinity and specificity for dopamine transporter sites in vitro and in vivo in laboratory animals. The goal of this study was the preparation and preliminary biological characterization of two new ligands based on the structure of WIN 35,428, the E and Z isomers of N-iodoallyl-2 beta -carbomethoxy-3 beta-(4-fluorophenyl)tropane (E and A IACFT). METHODS: E and Z IACFT were synthesized and radiolabeled with 125I. The ligands were characterized by in vitro assays of binding to dopamine and serotonin transporters and by autoradiography. RESULTS: Iodine-125-IACFT was prepared in > 60% radiochemical yield, and > 98% radiochemical purity. Specific activity was 1500 Ci/mmole. In vitro, E-IACFT showed higher affinity for dopamine transporter sites than WIN 35,428 (6.6 versus 11 nM) and better selectivity than RTI-55. The Z isomer was found to have much lower affinity. One hour after an intravenous injection of 125I IACFT in monkeys, ex vivo autoradiographs of the brain revealed high concentrations of tracer in dopamine rich regions such as the caudateputamen. The striatum-to-cerebellum, striatum-to-cortex and striatum-to-thalamus ratios were 10.8, 7.2 and 8.3. CONCLUSION: These result suggest that radiolabeled E-IACFT may be a useful radioligand for SPECT imaging of dopamine transporter sites. IACFT could prove to be extremely useful for the noninvasive evaluation of patients with early Parkinson's disease.

Synthesis of fluorine-18-labeled biotin derivatives: biodistribution and infection localization.

UNLABELLED: Recently there has been much interest in the exploitation of the high binding affinity of avidin/biotin as a means of targeting drugs and radionuclides for in vivo applications. We are interested in broadening the application of the avidin/biotin complex to PET. To this end we set out to prepare 18F-labeled biotin analogs. METHODS: Two 18F biotin derivatives, [3aS-(3a alpha,4 beta,6a alpha)]-hexahydro-2-oxo-1H-thieno[3,4- d]imidazole-4-(N-3-(1-[18F]fluoropropyl))pentanamide (1) and [3aS-(3a alpha,4 beta,6a alpha)]-tetrahydro-4-(5-(1-[18F]fluoropentyl)- 1H-thieno[3,4-d]imidazol-2(3H)-(2) were prepared with high specific activity (NCA) and evaluated for their potential in infection localization. RESULTS: Compound 1 binds to avidin and the biodistribution of these derivatives were studied in Escherichia coli infected rats. Half of the infected rats were treated with avidin 24 hr prior to intravenous injection of the 18F-labeled biotin analogs. Biotin 1, without avidin pretreatment, showed a selectivity of 6.08 +/- 1.12 for infection compared to normal muscle. With avidin pretreatment, selectivity increased slightly, giving an infection to normal muscle ratio of 6.39 +/- 0.96. In contrast, the biodistribution of biotin 2 indicated more binding to normal muscle with an infection to normal muscle ratio of 0.58 +/- 0.07. This lack of selectivity illustrates the importance of the side-chain amide group in infection localization. There was some defluorination of 1 and 2, as evidenced by increased 18F bone uptake after 60 min: 2.94 +/- 0.37 and 1.17 +/- 0.21 %IG/g +/- s.d., respectively. CONCLUSIONS: Biotin derivatives could be radiofluorinated with high specific activity. Biotin 1, is a potential positron tomography tracer for infection imaging.

Dopamine terminal loss and onset of motor symptoms in MPTP-treated monkeys: a positron emission tomography study with 11C-CFT.

We studied the time course of dopamine (DA) terminal loss in three macaca fascicularis injected with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) intravenously every 10-14 days for up to 389 days. Striatal DA terminal loss was monitored in vivo by positron emission tomography using 11C-CFT (WIN 35,428), a cocaine derivative that labels the DA transporter. The 11C-CFT uptake rate constant in the striatum of MPTP-treated monkeys decreased exponentially over time, with the putamen significantly more affected than the caudate. Spontaneous locomotor activity decreased in parallel with the decline of the 11C-CFT uptake rate; however, overt parkinsonian signs appeared only after the 11C-CFT uptake rate had declined to about 30% of the pretreatment values. We conclude that a long-term intermittent mode of administration of MPTP can lead to a pattern of terminal loss that closely resembles idiopathic Parkinson disease.

PET- and MRI-based assessment of glucose utilization, dopamine receptor binding, and hemodynamic changes after lesions to the caudate-putamen in primates.

In vivo physiological changes associated with striatal pathology were determined by measurement of glucose utilization, binding to D1 receptors and dopamine reuptake sites, regional blood flow, and behavior before and after unilateral quinolinate infusions into caudate-putamen in three nonhuman primates (Macaca fascicularis and Macaca mulatta). Following the quinolinate lesion, symptoms similar to those of Huntington's disease could be induced by dopamine agonist treatment. In addition, all animals showed a long-term decrease in glucose utilization in the caudate by [19F]fluoro-2-deoxy-D-glucose positron emission tomography (PET). At 4-6 weeks following the lesion the average decrease in glucose utilization in the caudate-putamen was between 40 and 50% of the prelesion values in primates with large lesions. Corresponding caudate-putamen regional blood volume in these animals showed a 61 and 74% decrease as studied by magnetic resonance imaging with somewhat smaller changes observed in an index of cerebral blood flow. The caudate-putamen uptake rate constants for D1 receptors reflected neuronal loss and decreased by an average 40 and 48%, as determined by 11C-labeled Schering compound (SCH 39 166) and PET. Dopamine reuptake sites and fibers assessed by the 11C-labeled cocaine analog, WIN 35 428 compound, and PET showed a temporary decrease in areas with mild neuronal loss and a long-term decrease in striatal regions with severe destruction. These results, which were consistent with behavioral changes and neuropathology seen at postmortem examination, can be related to in vivo physiological studies of Huntington's disease patients.

Imaging of activated natural killer cells in mice by positron emission tomography: preferential uptake in tumors.

Optimal delivery of immunologically active cells to target tissue(s) is important for improving adoptive immunotherapy of neoplastic diseases. By using positron emission tomography, we have measured the systemic distribution and tumor localization of locally injected, activated natural killer (NK) cells or nonactivated lymphocytes in the FSaII fibrosarcoma grown s.c. in the tail of C3H mice. Murine NK cells were isolated and expanded in the presence of interleukin 2 and collected at 5 to 7 days after culture. These cells were then washed and labeled with [11C]methyl iodide, a positron-emitting isotope. Ten million activated or nonactivated cells were injected into the lateral tail vein distal to the tumor over a period of 2 min, and the accumulation of counts in the tumor was monitored during the injection and at 30-60 min postinjection. There was no significant difference in the rate of accumulation of activated NK cells (685 +/- 264 (SE); n = 5) versus nonactivated splenic lymphocytes (595 +/- 105; n = 5) during the injection period. Whole body scans of the mice done at 30 min to 1 h postinjection showed that the number of activated cells retained within the tumor ranged from 4 to 30% (15.3 +/- 4.9%; n = 5) of the injected dose. Activated NK cells which were not retained by the tumor accumulated in the lungs, liver, and spleen. In contrast, from 3 to 4% (3.4 +/- 0.2%; n = 5) of nonactivated lymphocytes remained within the tumor by 1 h. Nonactivated cells were distributed more homogeneously throughout the systemic circulation than the activated cells, although these cells also demonstrated increased retention in the lungs, liver, and spleen. The present study demonstrates that positron emission tomography may be used to quantify the number of effector cells which accumulate within tumors and to determine their biodistribution. The retention of labeled cells within the tumor may also be used as a means of imaging the tumor. Finally, the preferential accumulation of effector cells in the tumor vasculature following local injection has useful implications for adoptive immunotherapy.

Cyclic variation of ultrasound backscatter in normal myocardium is view dependent: clinical studies with a real-time backscatter imaging system.

Real-time ultrasound backscatter imaging is a new method of evaluating relative integrated backscatter in a clinically applicable manner. The potential clinical utility of real-time backscatter imaging of diseased tissue depends on recognition of normal variations in cyclic backscatter when measured from different echocardiographic image orientations. The view dependence of cyclic backscatter variation was studied in normal human volunteers. In twenty normal male subjects (mean age 28 +/- 5 years) cyclic variation in integrated backscatter (diastolic minus systolic backscatter) was assessed in multiple left ventricular regions with four standard two-dimensional echocardiographic views (parasternal long-axis and short-axis views, and apical two-chamber and four-chamber views). M-mode backscatter imaging was performed from the standard parasternal long-axis view. Cyclic variation in backscatter was present in the septum only when imaged from the parasternal long-axis view (2.7 +/- 3.1 [standard deviation] decibels [dB], p less than 0.01 for diastole versus systole). The posterior wall of the left ventricle demonstrated cyclic variation of integrated backscatter when imaged from both the parasternal long-axis (4.6 +/- 1.6 dB, p less than 0.01) and short-axis views (2.8 +/- 2.2 dB, p less than 0.01). Cyclic variation in integrated backscatter was not demonstrated in inferoseptal, septal, or lateral wall regions when imaged from the parasternal short-axis view. The apical views did not demonstrate cyclic variation in integrated backscatter in any of the segments studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrasound integrated backscatter tissue characterization of remote myocardial infarction in human subjects.

To determine whether quantitative ultrasound tissue characterization differentiates normal myocardial regions from segments of remote infarction, 32 consecutive patients with a diagnosis of previous myocardial infarction were evaluated. Images were obtained in real time with a modified two-dimensional ultrasound system capable of providing continuous signals in proportion to the logarithm of integrated backscatter along each A line. In 15 patients, adequate parasternal long-axis images that delineated both normal and infarct segments were obtained with standard time-gain compensation. Image data were analyzed to yield both magnitude and delay (electrocardiographic R wave to nadir normalized for the QT interval) of the cyclic variation of backscatter. Cyclic variation was present in 55 of 56 normal myocardial sites, averaging (mean +/- SEM) 3.2 +/- 0.2 dB in magnitude and exhibiting a mean normalized delay of 0.87 +/- 0.03. The magnitude of cyclic variation in infarct segments was significantly reduced to 1.1 +/- 0.2 dB (42 sites), and the delay was markedly increased to 1.47 +/- 0.12 (21 sites) (p less than 0.0001 for both). In 20 of 42 infarct sites, no cyclic variation was detectable. Thus, ultrasound tissue characterization quantitatively differentiated infarct segments from normal myocardium in patients with remote myocardial infarction.

Development of a 12 element annular array transducer for realtime ultrasound imaging.

While the recent proliferation of ultrasound scanners based on annular array transducers has attracted widespread attention, very little published information is available on the physics, design criteria, and signal processing aspects of these instruments. In this paper, the first of a two part report, we describe the development and characterization of an annular array transducer for realtime medical imaging. Theoretical modeling of the pulsed fields of annular arrays is used to study and optimize array parameters. The factors which affect resolution and contrast in imaging--beam width, sidelobe levels, number of annuli, depth of field, and delay quantization--are discussed. A 12 element, 4.5 MHz, 30 mm design is adopted. Theoretical predictions showed excellent agreement with device measurements over a range of f-numbers (local/length/diameter) from f/1 to f/6.7 (30 to 200 mm range). Focusing to f/1 is an important advance in the state-of-the-art. A two transmit zone, dynamic receive configuration of array operation to exploit the f/1 focusing ability is proposed for realtime imaging.

Quantitative ultrasonic tissue characterization with real-time integrated backscatter imaging in normal human subjects and in patients with dilated cardiomyopathy.

We have shown previously that the physical properties of myocardium in dogs can be characterized with quantitative ultrasonic integrated backscatter and that interrogation of the tissue with ultrasound can delineate cardiac cycle-dependent changes in ultrasonic backscatter in normal tissue that disappear with ischemia and reappear with reperfusion if functional integrity is restorable. To determine whether this approach can be applied to man, we implemented an automatic gain compensation and continuous data acquisition system to characterize myocardium with quantitative ultrasonic backscatter and to detect cardiac cycle-dependent changes in real time. We developed a two-dimensional echocardiographic system with quantitative integrated backscatter imaging capabilities for use in human subjects that can automatically differentiate ultrasonic signals from blood as opposed to those obtained from tissue and adjust the slope of the gain compensation appropriately. Real-time images were formed from a continuous signal proportional to the logarithm of the integrated backscatter along each A-line. In our initial investigation, 15 normal volunteers (ages 17 to 40 years, heart rates 44 to 88 beats/min) and five patients with dilated cardiomyopathy (ages 22 to 52, heart rates 82 to 120 beats/min) were studied with conventional parasternal long-axis echocardiographic views. Diastolic-to-systolic variation of integrated backscatter in the interventricular septum and left ventricular posterior wall was seen in each of the normal subjects averaging 4.6 +/- 1.4 dB (SD) and 5.3 +/- 1.5 dB (n = 127 sites), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)