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H J Machulla

Publications and source records attributed to H J Machulla.

At least 19 recordsLinked to original sources
PubMed2003

On biologically conformal boost dose optimization.

A method is described that allows the inclusion of biological imaging data in the optimization of intensity-modulated radiotherapy to produce dose boosts that conform with target subvolumes of potentially reduced radiosensitivity. The biological image (e.g. PET, fMRI, etc) is transformed into a dose efficiency distribution using a piecewise linear calibration function with a prescribed maximum boost factor. Instead of dose alone, the cost function of the optimization algorithm depends on the product of the physical dose times dose efficiency. An example case of a base-of-tongue tumour which was imaged with the hypoxia tracer fluoro-misonidazole is presented, showing the excellent capability of IMRT to produce dose distributions that conform to spatially variable dose prescriptions.

Algorithms↗
PubMed2001

Neuroimaging in alcoholism: ethanol and brain damage.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The co-chairs were Karl Mann and Ingrid Agartz. The presentations were (1) Neuropathological changes in alcohol-related brain damage, by Clive Harper; (2) Regional brain volumes including the hippocampus and monoamine metabolites in alcohol dependence, by Ingrid Agartz, Susan Shoaf, Robert R, Rawlings, Reza Momenan, and Daniel W Hommer; (3) Diffusion tensor abnormalities in imaging of white matter alcoholism, by Adolf Pfefferbaum and Edith V. Sullivan; (4) Use of functional MRI to evaluate brain activity during alcohol cue exposure in alcoholics: Relationship to craving, by Raymond F. Anton, David J. Drobes, and Mark S. George; and (5) mu-Opiate receptor availability in alcoholism: First results from a positron emission tomography study, by Karl Mann, Roland Bares, Hans-Juergen Machulla, Goetz Mundle, Matthias Reimold, and Andreas Heinz.

Alcoholism↗
PubMed2001

Assessment of porcine bone metabolism by dynamic.

UNLABELLED: The aim of this study was to quantify regional bone blood flow and [(18)F]fluoride ion influx with [(18)F]fluoride ion PET and correlate the results with specific static and dynamic indices of bone metabolism in healthy pigs. METHODS: During continuous ventilation (fractional concentration of oxygen in inspired gas = 0.3), dynamic PET scans 120 min in duration were obtained for 9 mini pigs after intravenous injection of 10.0 +/- 1.2 MBq (mean +/- SD) of [(18)F]fluoride ion per kilogram of body weight. Iliac crest bone biopsies were performed immediately before the PET scan to determine static and dynamic indices of bone metabolism (i.e., the mineral apposition rate) by bone histomorphometry. Kinetic rate constants describing influx (K(1)) and efflux (k(2)) of [(18)F]fluoride as well as chemisorption and incorporation of [(18)F]fluoride (k(3)) and reverse transport (k(4)) were determined for 6 vertebral bodies in each animal. Blood flow estimates (f) were derived from K(1) values corrected for the permeability-surface area product using a previously derived correction algorithm. A rate constant describing the net forward transport rate of fluoride (K(i)) and the fluoride volume flux (K(flux)) derived from a 2-tissue-compartment model was calculated and compared with the results of Patlak graphic analysis (K(pat)). RESULTS: A significant correlation was found between mineral apposition rate and K(i) (P < 0.005), K(flux) (P < 0.01), K(pat), K(1), and f (P < 0.05). The values of f, K(i), K(flux), and K(pat) did not correlate significantly with other static or dynamic histomorphometric indices or with age, serum alkaline phosphatase, or parathyroid hormone levels. The values of f and K(i) correlated linearly (y = 0.023 + 0.32x; r(2) = 0.74; P < 0.001). CONCLUSION: PET bone studies using [(18)F]fluoride ion provide quantitative estimates of bone blood flow and metabolic activity that correlate with histomorphometric indices of bone formation in the normal bone tissue of the mini pig. Therefore, it seem reasonable to assume that [(18)F]fluoride ion PET can reduce the number of invasive bone biopsies, thus facilitating follow-up of patients with metabolic bone diseases.

Animals↗
PubMed2000

Dependency of the [18F]fluoromisonidazole uptake on oxygen delivery and tissue oxygenation in the porcine liver.

We have previously shown that the accumulation of fluorine-18-labeled fluoromisonidazole ([(18)F]FMISO) is inversely correlated to tissue oxygenation, allowing the quantification of porcine liver tissue hypoxia in vivo. We determined the activity from administered [(18)F]FMISO in relation to the hepatic oxygen availability and the partial pressure of oxygen in tissue (tPO(2)) to define a critical oxygen delivery on a regional basis. [(18)F]FMISO was injected 2 h after onset of regional liver hypoxia due to arterial occlusion of branches of the hepatic artery in 10 domestic pigs. During the experimental procedure the fractional concentration of inspired oxygen (FiO(2)) was set to 0.67 in group A ( N=5) and to 0.21 in group B ( N=5) animals. Immediately before sacrifice, the tPO(2) was determined in normal flow and flow-impaired liver segments. The standardized uptake values (SUV) for [(18)F]FMISO was calculated from 659 single tissue samples obtained 3 h after injection of approximately 10 MBq/kg body weight [(18)F]FMISO and was compared with the regional total hepatic oxygen delivery (DO(2)) calculated from the regional arterial and portal venous flow (based on (141)Ce- and (99m)Tc-microspheres measurements) and the oxygen content of the arterial and portal venous blood. In 121 tPO(2)-measured liver tissue samples, the mean DO(2) was significantly decreased in occluded liver tissue samples [group A: 0.063 (0.044-0.089); group B: 0.046 (0.032-0.066)] compared to normal flow segments [group A: 0.177 (0.124-0.252); group B: 0.179 (0.128-0.25) mL x min(-1) x g(-1); geometric mean (95% confidence limits); p < 0.01 in group A and p < 0.001 in group B]. The tPO(2) of occluded segments [group A: 5.1 (3.2-8.1); group B: 3.9 (2.4-6.2) mm Hg] was significantly decreased compared to normal flow segments [group A: 20.2 (12.6-32.5); group B: 22.4 (14.3-35.2) mm Hg; p < 0.01 in group A and p < 0.001 in group B]. Three hours after [(18)F]FMISO administration, the mean [(18)F]FMISO SUV determined in tPO(2)-measured occluded segments was significantly higher [group A: 4.08 (3.12-5.34), group B: 5.43 (4.14-7.13)] compared to normal liver tissue [group A: 1.57 (1.2-2.06), group B: 1.5 (1.16-1.93); p < 0.001 for both groups]. The [(18)F]FMISO SUV allowed prediction of the tPO(2) with satisfying accuracy in hypoxic regions using the exponential regression curve [[(18)F]FMISO=1.05+6.7((-0.117 tPO(2))); r(2)=0.75; p < 0.001]. In addition, regardless of ventilation conditions, a significant exponential relationship between the DO(2) and the [(18)F]FMISO SUV was found ( r(2)=0.39, p < 0.001). Our results suggest that the reduction of the oxygen delivery below the critical range of 0.1-0.11 mL x min(-1) x g(-1) regularly causes liver tissue hypoxia. The severity of hypoxia is reflected by the [(18)F]FMISO accumulation and allows the in vivo estimation of the tPO(2) in hypoxic regions.

Animals↗
PubMed1998

Imaging proliferation in vivo with [F-18]FLT and positron emission tomography.

Positron emission tomography (PET) is now regularly used in the diagnosis and staging of cancer. These uses and its ability to monitor treatment response would be aided by the development of imaging agents that can be used to measure tissue and tumor proliferation. We have developed and tested [F-18]FLT (3'-deoxy-3'-fluorothymidine); it is resistant to degradation, is retained in proliferating tissues by the action of thymidine kinase 1 (TK), and produces high-contrast images of normal marrow and tumors in canine and human subjects.

Animals↗
PubMed1998

Blood flow measurements with [(15)O]H2O and [18F]fluoride ion PET in porcine vertebrae.

A dual positron emission tomography (PET) tracer study with [18F]fluoride and the freely diffusible tracer [(15)O]H2O was performed to measure the capillary transport of [18F]fluoride and to evaluate the potential of [18F]fluoride ion PET to quantitate bone blood flow. Under the condition of a high predictable single-pass extraction fraction (E(F)) for [18F]fluoride, the [18F]fluoride ion influx transport constant (K1F), derived from kinetic [18F]fluoride ion PET measurements, can be used to estimate bone blood flow. Bone blood flow was measured in vertebral bodies by dynamic [(15)O]H2O PET during continuous ventilation with N2O, O2, and Isoflurane (FiO2 = 0.3) in seven adult mini pigs, followed by dynamic [18F]fluoride ion PET. The mean blood flow measured by [(15)O]H2O (FlowH2O) was 0.145 +/- 0.047 ml x minute(-1) x ml(-1) and the mean K1F was 0.118 +/- 0.031 ml x minute(-1) x ml(-1), respectively (mean +/- SD). Regional analysis showed excellent agreement between FlowH2O and K1F at low flow and a significant underestimation of flow by K1F relative to FlowH2O in regions of normal and elevated flow. The observed relationship between parameters followed the Renkin-Crone distribution. The permeability-surface product was determined as 0.25 minute(-1) for vertebral bodies consisting of a mixture of trabecular and cortical bone. We conclude that [18F]fluoride ion PET can be used to estimate bone blood flow in low and normal flow regions, as long as the flow dependency of the E(F) is taken into consideration. Above blood flow values of 0.2 to 0.35 ml x minute(-1) x ml(-1), the magnitude of K1F is increasingly independent on blood flow because diffusion limits tracer transport.

Animals↗
PubMed1996

[Examination of psychological functions by functional imaging with positron emission tomography and magnetic resonance imaging].

Changes in regional cerebral blood flow (rCBF) during experimentally modified psychological activation can be measured using radioactive ligands with positron emission tomography (PET) and using magnetic resonance principles with functional magnetic resonance imaging (fMRI). With PET it is possible to determine not only rCBF, but also metabolic changes, as well as the density and binding of several neuroreceptors. This can be done in conjunction with psychological and pharmacological challenge. fMRI is an imaging technique for perfusion-based signal intensities of the brain which does not involve radioactivity and gives better anatomical and temporal resolution than PET. Under appropriate experimental conditions, subjects' behavior and experience can be modified while they are lying in a tomograph. These experiments can be used for the scientific investigation of cognitive constructs such as memory and attention, or emotional processes. In this review, both functional neuroimaging techniques are assessed.

Arousal↗
PubMed1991

Fatty acid uptake in normal human myocardium.

Fatty acid binding protein has been found in rat aortic endothelial cell membrane. It has been identified to be a 40-kDa protein that corresponds to a 40-kDa fatty acid binding protein with high affinity for a variety of long chain fatty acids isolated from rat heart myocytes. It is proposed that this endothelial membrane fatty acid binding protein might mediate the myocardial uptake of fatty acids. For evaluation of this hypothesis in vivo, influx kinetics of tracer-labeled fatty acids was examined in 15 normal subjects by scintigraphic techniques. Variation of the plasma fatty acid concentration and plasma perfusion rate has been achieved by modulation of nutrition state and exercise conditions. The clinical results suggest that the myocardial fatty acid influx rate is saturable by increasing fatty acid plasma concentration as well as by increasing plasma flow. For analysis of these data, functional relations describing fatty acid transport from plasma into myocardial tissue in the presence and absence of an "unstirred layer" were developed. The fitting of these relations to experimental data indicate that the free fatty acid influx into myocardial tissue reveals the criteria of a reaction on a capillary surface in the vicinity of flowing plasma but not of a reaction in extravascular space or in an unstirred layer and that the fatty acid influx into normal myocardium is a saturable process that is characterized by the quantity corresponding to the Michaelis-Menten constant, Km, and the maximal velocity, Vmax, 0.24 +/- 0.024 mumol/g and 0.37 +/- 0.013 mumol/g(g.min), respectively. These data are compatible with a nondiffusional uptake process mediated by the initial interaction of fatty acids with the 40-kDa membrane fatty acid binding protein of cardiac endothelial cells.

Animals↗
PubMed1990

Tracer kinetics of 15-(ortho-123/131I-phenyl)-pentadecanoic acid (oPPA) and 15-(para-123/131I-phenyl)-pentadecanoic acid (pPPA) in animals and man.

The human myocardium retains oPPA as opposed to pPPA. Therefore turnover of oPPA was compared with that of pPPA in rat hearts and in man, the latter by using substrates double-labeled with 123/131I and 14C. Moreover, substrate binding to coenzyme-A was tested in vitro. In rats, oPPA remained mainly in the pool of free fatty acids, as opposed to pPPA, which was metabolized by mitochondrial beta-oxidation. Binding to coenzyme-A at maximum was 62% for oPPA, 81% for pPPA and 90% for palmitic acid. In man, after i.v. and intracoronary injection of double-labeled oPPA, the two radionuclides reappeared together in venous blood and in coronary sinus respectively, in an unchanged ratio but at a significantly lower rate than with pPPA. It can be concluded that oPPA is bound to coenzyme-A and is retained in the cytosolic lipid pool, while pPPA is metabolized by mitochondrial beta-oxidation. A dual-tracer application of oPPA and pPPA has the potential of being a specific probe for the function of the carnitine shuttle.

Animals↗
PubMed1989

High specific activity 15-(p-[123I]iodophenyl)pentadecanoic acid.

An improved labeling procedure for 15-(p-[123I]iodophenyl)pentadecanoic acid (IPPA) is reported. The exchange labeling yield was greater than 95%. The radiochemical yield is influenced by the presence of sodium. The major advantage of this method is that very high specific activity i.e. upto 190 mCi/mg labeled IPPA can be prepared.

Iodine Radioisotopes↗
PubMed1988

Regional myocardial free fatty acid extraction in normal and ischemic myocardium.

The rate constant for free fatty acid influx (k1) was studied in normal and ischemic myocardium. In 15 normal subjects and 30 patients with coronary artery disease, 201Tl and 15-(p-123I-iodophenyl)-pentadecanoic acid (IPPA) were administered during exercise under fasting conditions and at rest. In 10 patients, the study was repeated after percutaneous transluminal coronary angioplasty; in three patients, the study was repeated after infarction. The initial accumulation of IPPA, related to that of 201Tl (both background and crossover corrected), was used for determinations of the regional rate constant of IPPA influx into myocardial tissue (k1*). In normal subjects, no significant differences in k1* between major myocardial segments were found; the average value of k1* was 0.57 +/- 0.13/min (mean +/- SD) at rest and 0.42 +/- 0.06/min at exercise (average workload, 123 +/- 47 W). With increasing free fatty acid plasma concentration and perfusion, free fatty acid influx increased in a saturable fashion. The Michaelis-Menten constant (KM*) and the maximal velocity (Vmax*) for IPPA influx into myocardial tissue were estimated to be 470 nmol/g and 430 nmol/g.min, respectively. In ischemic areas, k1* was reduced to 57 +/- 18% of k1* value in nonaffected segments. The areas were larger than those showing reduced 201Tl uptake. Preinfarction and postinfarction studies showed that the size of 201Tl defects in postinfarction images corresponded with the size of the area with reduced k1* observed in preinfarction scintigrams. Revascularization led to an increase of 201Tl uptake and to normalization of k1*.

Coronary Disease↗
PubMed1988

Double-nuclide study of the myocardium using 201Tl and 123I-labeled fatty acids in non-ischemic myocardial diseases.

Metabolic impairment and perfusion abnormalities are known to occur in hypertensive heart disease (HHD) and in cardiomyopathies. Free fatty acid (FFA) extraction is severely inhibited in a number of pathobiochemical reactions. This parameter was assessed using the radiolabeled FFA analogue 123I-(p-iodo-phenyl-)-pentadecanoic acid (IPPA) and 201Tl as perfusion marker, both of them injected at maximal physical workload. The regional extraction fraction of IPPA (IPPA-EF) was estimated by relating the regional IPPA and 201Tl uptake to each other. In HHD (normal coronary arteries) with posterior wall thickness less than or equal to 12 mm IPPA-EF was 77 +/- 18% (SD) in septum and 92 +/- 17% in the posterolateral wall (N = 13), with thickness of greater than 12 mm 60 +/- 23% in septum and 61 +/- 20% in the posterolateral wall (N = 8) when compared with IPPA-EF in normal subjects (= 100%, N = 9). In hypertrophic cardiomyopathy (HCM) IPPA-EF averaged 51 +/- 20% in septum and 87 +/- 10% in the posterolateral wall (N = 11). In these patient groups no systematic regional changes in 201TI uptake were observed. In dilated cardiomyopathy (DCM) both IPPA-EF and 201Tl uptake showed distinct regional variations and a great interindividual variability with a mean IPPA-EF reduction of 12% (N = 9). Thus, IPPA uptake in primarily non-ischemic myocardial disease may already be compromised when 201Tl uptake is unchanged. The double-nuclide method for IPPA-EF determination allows to eliminate the influence of flow in FFA imaging and enhances the potential of scintigraphy in the differential diagnosis of HHD versus coronary artery disease.

Cardiomyopathies↗
PubMed1986

Effect of myocardial perfusion and metabolic interventions on cardiac kinetics of phenylpentadecanoic acid (IPPA) I 123.

The effect of regional myocardial perfusion and flow-independent adrenergic stimulation, as well as lactate-mediated inhibition of cardiac lipolysis, on cardiac IPPA uptake and metabolism was examined in canine hearts (flow studies) and in the isolated perfused Langendorff rat heart (metabolic interventions). In both normal and ischaemic myocardium, local perfusion is a major determinant of cardiac IPPA uptake. In pacing-induced hyperaemia, the strict flow-dependence of cardiac IPPA uptake is not preserved. Adrenergic stimulation raises the rate of oxidation of both palmitic acid 14C and IPPA. This change is reflected by increased metabolite production released into the perfusate and radioactivity clearance recorded externally. Lactate in high concentrations exerts the opposite effect on cardiac free fatty acid oxidation. IPPA is stored in this condition preferentially in tissue phospholipids and triglycerides.

Animals↗
PubMed1986

Radioiodinated fatty acids for cardiological diagnosis.

The development of fatty acids labelled with iodine-123 is reviewed. The variety of methods for producing 123I and introducing radioiodine into the molecule is discussed and the important points of the biochemical background are recalled with the aim of finding a broad application for 123I-labelled fatty acids. The results of the pharmacokinetic studies and biochemical analyses are presented as they prove that both 17-123I-heptadecanoic acid (IHA) and 15-(p-123I-phenyl)pentadecanoic acid (IPPA) exhibit analogous behaviour to that of the naturally occurring fatty acids. Clinical applications demonstrated two fields of importance: applications solely for imaging the heart and assessment of myocardial turnover rates of fatty acids for functional diagnosis. Moreover, very recent studies show that the provision of information about prognosis of myocardial diseases and the applied cardiological therapy appear to be possible.

Animals↗
PubMed1986

15-(ortho-123I-phenyl)-pentadecanoic acid, a new myocardial imaging agent for clinical use.

The result of previous experiments in rodents indicated different kinetics for the para- and ortho-isomers of 15-(iodophenyl)-pentadecanoic acid (p-IPPA, o-IPPA), with o-IPPA showing an enhanced rate of washout. To test the relevance of this phenomenon for clinical diagnosis, 15 fasting male patients with confirmed coronary heart disease (1-VD/7, 2-VD/4, 3-VD/4) were investigated under exercise. Serial images were recorded at a rate of 3 frames min-1 for 70 to 90 min, corrected for tracer in blood and compared with thallium-201 images obtained from these patients within less than 2 weeks. Time-activity curves were also taken from the peripheral blood. Ortho-IPPA was well taken up by healthy myocardium and, contrary to rodents, retained with elimination half times longer than 200 min. A decreased myocardial uptake was seen which was very similar to the pattern obtained with thallium. Ortho-IPPA was eliminated from the blood to less than 10% at 4 min. Almost all radioactivity was in the organic phase (greater than 95% at 5 min) and chromatography showed only one major peak (o-IPPA) indicative of minimal organic catabolism.

Adult↗
PubMed1985

Metabolism of 15 (p 123I iodophenyl-)pentadecanoic acid in heart muscle and noncardiac tissues.

The uptake and turnover of omega(p 123I iodophenyl-)pentadecanoic acid (I-PPA), a radioiodinated free-fatty-acid analog, was examined in the heart, lung, liver, kidneys, spleen, and skeletal muscle of rats. At 2 min post injection, a high cardiac uptake of 4.4% dose per gram had already been achieved; this was followed by a rapid, two-component, tracer clearance. The kinetics of tissue concentrations of labeled hydrophilic catabolites indicated a rapid oxidation of I-PPA and the subsequent washout of I-PPA catabolites from heart-muscle tissue. The fractional distribution of the labeled cardiac lipids compared favorably with previously reported values for 3H-oleic- or 14C-palmitic-acid-labeled myocardial lipids. Typical patterns of I-PPA metabolism were observed in tissues depending on primary fatty-acid oxidation, lipid metabolism regulation, or I-PPA-catabolite excretion. The tissue concentrations and kinetics of I-PPA and its metabolites in the heart muscle indicated that general pathways of cardiac-lipid metabolism are traced by this new gamma-emitting isotope-labeled radiopharmaceutical.

Animals↗