Measurement of absolute bone blood flow by positron emission tomography

A method of measuring bone blood flow has been developed using ¹⁸F sodium fluoride and positron emission tomography. The blood flow levels are in line with those obtained experimentally from microsphere embolisation. This investigative method could be applied to elucidate a number of clinical questions involving bone perfusion.     

The preparation of 11C-labelled fluoromethane for the study of regional cerebral blood flow using positron emission tomography

Fluoromethane, previously labelled with ¹⁸F and used as a tracer in the measurement of regional cerebral blood flow, was ¹¹C-labelled by the reaction of ¹¹C-methyl iodide with tetraethylammonium fluoride. Sufficient quantities of radiotracer were prepared with a minimum amount of handling from 15 min target irradiations in the ¹⁴N(p, ) ¹¹C reaction. Total synthesis time was 25 min from end-of-bombardment, allowing serial blood flow measurements 30 min apart. The use of ¹¹C-fluoromethane as a cerebral blood flow tracer in positron emission tomography is discussed.     

Xenon effects on regional cerebral blood flow assessed by 15O-H2O positron emission tomography: Implications for hyperpolarized xenon MRI

Subjective and physiologic effects of 33% inhaled Xe were measured with ¹⁵O-water positron emission tomography (PET) in 3 subjects at rest and during visual stimulation. The procedure was well tolerated. Robust functional activations of the visual cortex were obtained after xenon (Xe) inhalation as well as air breathing. However, Xe inhalation was followed by smaller size, but significant decreases of regional cerebral blood flow (rCBF) in visual cortex relative to the air-breathing baseline, both during visual stimulation and at rest. No such decreases were found in other sensory or motor regions.     

Quantitative measurement of regional myocardial blood flow in patients with coronary artery disease by intravenous injection of13N-ammonia in positron emission tomography

Measurement of myocardial blood flow with¹³N-ammonia, a technique previously employed sucessfully in animal experiments, was introduced into clinical use to study patients with coronary artery disease. This advance has become possible by the development of a high resultion gated scan positron emission tomographic (PET) scanner equipped with a real time decay correction mechanism, HEADTOME-IV. The information obtainable includes myocardial size and wall motion as well as the absolute quantity of blood flow in various myocardial regions. The technique is simple but requires continuous arterial blood withdrawal for calculation of the arterial input function time integral. The alternative to this technique, i.e. the computation of intra left ventricular blood pool activity by PET is also discussed.     

Haemodynamics and oxygen metabolism in patients after reversible ischaemic attack or minor ischaemic stroke assessed with positron emission tomography

Summary Regional cerebral blood flow (CBF), blood volume (CBV) and oxygen metabolic rate (CMRO2) were evaluated and compared among normals, patients with recent reversible ischaemic attacks (RIAs) and patients with chronic minor infarction using positron emission tomography. Average CBF together with CMRO2 significantly decreased in the infarction group in the middle cerebral artery territory of the affected hemisphere while the mean values for RIAs were intermediate between the other two groups. CBV also reduced, however it was more preserved compared to flow as seen in decreased CBF/CBV values. Significant interhemispheric difference was found in CBF/CBV ratio, but it did not clearly correlate with OEF changes. Higher OEF was noted only in the restricted brain regions of RIAs where CBF showed large hemispheric asymmetry. However, in other regions, the coupled decline of blood flow and metabolism was found which suggests tissue damage or neuronal cell loss in the brain with previous RIA symptoms.     

Imaging metastatic testicular germ cell tumours with18FDG positron emission tomography: prospects for detection and management

The aim of this study was to investigate the role of positron emission tomography (PET) with [¹⁸F]fluoro-2-deoxyglucose (¹⁸FDG) in metastatic testicular germ cell tumours. Twenty-one patients with stage II–IV testicular germ cell tumours were imaged by PET with a multiwire proportional chamber PET system and¹⁸FDG. Avid¹⁸FDG uptake was seen in metastatic disease from primary seminoma and malignant teratoma. Normal tissue uptake was seen in differentiated teratoma or necrotic, fibrotic tissue.¹⁸FDG standard uptake values and tumour to normal tissue ratios were 6.0±1.4 and 1.7±0.4 (mean ± 1SD), respectively, for malignant tissue. Reduction of¹⁸FDG tumour to normal tissue ratios from pre-treatment to on-treatment scans was predictive of response (n=3). No significant reduction in¹⁸FDG uptake was seen in patients not responding to therapy (n=2). These results suggest a role for¹⁸FDG PET in the detection and management of metastatic testicular germ cell tumours.     

Assessment of pathophysiology of stroke by positron emission tomography

In stroke patients, multitracer positron emission tomography (PET) permits the assessment of acute changes in regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen consumption (rCMRO₂) and glucose metabolism (rCMR_gl), which are the initial steps in the complex molecular and biochemical process leading to ischaemic cell damage. While early infarcts exhibit low flow and oxygen consumption, increased oxygen extraction fraction (OEF) due to preserved metabolism at reduced flow suggests viability of tissue. However, most initially viable tissue will be metabolically deranged and will become necrotic in the further course; only in a few instances do these tissue compartments recover to normal function. Increased glucose uptake at reduced oxygen supply induces non-oxidative glycolysis with noxious lactacidosis, whereas hyperperfusion beyond the metabolic demand is of controversial effect. In subacute or chronic states after ischaemia reduced flow can be compensated by increased blood volume; when perfusional reserve is exhausted, oxygen extraction increases. Such findings may guide therapeutic decisions and predict the severity of permanent deficits. Functional deactivation of tissue remote from the lesion is found regularly as a sign of damaged connecting pathways. Flow and metabolic studies during the performance of specific tasks help to detect alternative functional loops and may yield prognostic information. Repeat studies in the course of stroke are employed for the evaluation of therapeutic strategies targeted to improve reperfusion or to effect metabolic or biochemical alterations. In the future PET may gain additional clinical importance when patients are selected for elective treatment according to the prevailing pathophysiological pattern. Correspondence to: W.-D. Heiss     

Database of normal human cerebral blood flow, cerebral blood volume, cerebral oxygen extraction fraction and cerebral metabolic rate of oxygen measured by positron emission tomography with 15O-labelled carbon dioxide or water, carbon monoxide and oxygen: a multicentre study in Japan

Measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO₂) by positron emission tomography (PET) with oxygen-15 labelled carbon dioxide (C¹⁵O₂) or ¹⁵O-labelled water (H₂ ¹⁵O), ¹⁵O-labelled carbon monoxide (C¹⁵O) and ¹⁵O-labelled oxygen (¹⁵O₂) is useful for diagnosis and treatment planning in cases of cerebrovascular disease. The measured values theoretically depend on various factors, which may differ between PET centres. This study explored the applicability of a database of ¹⁵O-PET by examining between-centre and within-centre variation in values. Eleven PET centres participated in this multicentre study; seven used the steady-state inhalation method, one used build-up inhalation and three used bolus administration of C¹⁵O₂ (or H₂ ¹⁵O) and ¹⁵O₂. All used C¹⁵O for measurement of CBV. Subjects comprised 70 healthy volunteers (43 men and 27 women; mean age 51.8±15.1 years). Overall mean±SD values for cerebral cortical regions were: CBF=44.4±6.5 ml 100 ml^–1 min^–1; CBV=3.8±0.7 ml 100 ml^–1; OEF=0.44±0.06; CMRO₂=3.3±0.5 ml 100 ml^–1 min^–1. Significant between-centre variation was observed in CBV, OEF and CMRO₂ by one-way analysis of variance. However, the overall inter-individual variation in CBF, CBV, OEF and CMRO₂ was acceptably small. Building a database of normal cerebral haemodynamics obtained by the¹⁵O-PET methods may be practicable.     

Basal and hyperaemic myocardial blood flow in regionally denervated canine hearts: an in vivo study with positron emission tomography

Purpose Positron emission tomography (PET) studies in patients with diabetic autonomic neuropathy (DAN) have demonstrated the impact of this disease on cardiac sympathetic innervation and myocardial blood flow (MBF). To investigate the effects of selective partial sympathetic denervation of the left ventricle (LV) on baseline and hyperaemic MBF, we measured myocardial presynaptic catecholamine re-uptake (uptake-1), β-adrenoceptor (β-AR) density and MBF non-invasively by means of PET in a canine model of regional sympathetic denervation. Methods In 11 anaesthetised dogs, the sympathetic nerves of the free wall and septum of the LV were removed by means of dissection and phenol painting. Three weeks later, the animals were studied with PET. MBF was measured at baseline and following i.v. adenosine (140 μg kg⁻¹ min⁻¹) and dobutamine (20 μg kg⁻¹ min⁻¹) using¹⁵O-labelled water. Sympathetic denervation was confirmed by an 80±12% decrease in the volume of distribution (V_d) of [¹¹C]hydroxyephedrine (HED) compared with innervated regions. Myocardial β-AR density was measured using [¹¹C]CGP12177. Results Innervated and denervated regions showed no differences in MBF at baseline and during adenosine or dobutamine. [¹¹C]HED V_dwas inversely correlated with MBF in both regions at baseline, and the correlation was lost during hyperaemia in denervated regions. However, for any given value of MBF, [¹¹C]HED V_dwas significantly lower in the denervated regions. β-AR density was comparable in denervated and innervated regions (17.9±4.2 vs 18.4±3.3 pmol g⁻¹;p=NS). Conclusion In this experimental model, selective, regional sympathetic denervation of the LV, which results in a profound reduction in [¹¹C]HED V_d, did not affect baseline or hyperaemic MBF. In addition, we demonstrated that, under baseline conditions, there was a significant inverse correlation between [¹¹C]HED V_dand MBF in both denervated and innervated regions.     

Quantitative assessment of regional myocardial blood flow using oxygen-15-labelled water and positron emission tomography: a multicentre evaluation in Japan

Recently, a method has been proposed for the quantitative measurement of regional myocardial blood flow (MBF) using oxygen-15-labelled water and positron emission tomography (PET). A multicentre project was organized with the intention of evaluating the accuracy of this method, particularly as a multicentre clinical investigative tool. Each of seven institutions performed PET studies on more than five normal volunteers following a specified protocol. The PET study included a transmission scan, a ¹⁵O-carbon monoxide static scan and a ¹⁵O-water dynamic scan, thereby yielding MBF values which should have been independent of the spatial resolution of the PET scanner employed. Fifty-three subjects (aged 20–63 years, mean±SD 36±12 years) were studied at rest, and 31 of these subjects were also studied after dipyridamole in five institutions. Inter-institution consistency and intra-subject variation in MBF values were then evaluated. MBF averaged for all subjects was 0.93±0.34 ml min^–1 g^–1 at rest and 3.40±1.73 ml min^–1 g^–1 after the administration of dipyridamole, and the flow reserve (defined as the ratio of the two MBF values) was 3.82±2.12; these values are consistent with previous reports. Resting MBF values were significantly correlated with the heart rate–blood pressure product (RPP) (y=0.31+6.56E^-5 x, P<0.010), and RPP was in resting MBF observed in all institutions was well explained by the age-dependent RPP. No significant difference was observed in resting MBF among the institutions. Except in one institution, no significant difference was seen in dipyridamole MBF or myocardial flow reserve. No significant difference was found among the myocardial segments. Regional variation was reasonably small in five institutions, but was not acceptable in two institutions, which was attributed to the scanner performance. These observations suggest that the ¹⁵O-water PET technique is useful for a multicentre clinical study if the PET scanner can provide time-activity data with good count statistics. Received 25 April and in revised form 30 August 1999     

Estimation of intersubject variability of cerebral blood flow measurements using MRI and positron emission tomography

Purpose:

To investigate the within and between subject variability of quantitative cerebral blood flow (CBF) measurements in normal subjects using various MRI techniques and positron emission tomography (PET).

Materials and Methods:

Repeated CBF measurements were performed in 17 healthy, young subjects using three different MRI techniques: arterial spin labeling (ASL), dynamic contrast enhanced T1 weighted perfusion MRI (DCE) and phase contrast mapping (PCM). All MRI measurements were performed within the same session. In 10 of the subjects repeated CBF measurements by ¹⁵O labeled water PET had recently been performed. A mixed linear model was used to estimate between subject (CV_betw) and within subject (CV_with) coefficients of variation.

Results:

Mean global CBF, CV_betw and CV_with using each of the four methods were for PCM 65.2 mL/100 g/min, 17.4% and 7.4%, for ASL 37.1 mL/100 g/min, 16.2% and 4.8%, for DCE 43.0 mL/100 g/min, 20.0%, 15.1% and for PET 41.9 mL/100 g/min, 16.5% and 11.9%, respectively. Only for DCE and PCM a significant positive correlation between measurements was demonstrated.

Conclusion:

These findings confirm large between subject variability in CBF measurements, but suggest also that in healthy subjects a subject‐method interaction is a possible source of between subject variability and of method differences. J. Magn. Reson. Imaging 2012;35:1290–1299. © 2012 Wiley Periodicals, Inc.     

Resting state rCBF mapping with single-photon emission tomography and positron emission tomography: magnitude and origin of differences

Single-photon emission tomography (SPET), using technetium-99m hexamethylpropylene amine oxime, and positron emission tomography (PET), using oxygen-15 butanol were compared in six healthy male volunteers with regard to the mapping of resting state regional cerebral blood flow (rCBF). A computerized brain atlas was utilized for 3D regional analyses and comparison of 64 selected and normalized volumes of interest (VOIs). The normalized mean rCBF values in SPET, as compared to PET, were higher in most of the Brodmann areas in the frontal and parietal lobes (4.8% and 8.7% respectively). The average differences were small in the temporal (2.3%) and occipital (1.1%) lobes. PET values were clearly higher in small VOIs like the thalamus (12.3%), hippocampus (12.3%) and basal ganglia (9.9%). A resolution phantom study showed that the in-plane SPET/PET system resolution was 11.0/7.5 mm. In conclusion, SPET and PET data demonstrated a fairly good agreement despite the superior spatial resolution of PET. The differences between SPET and PET rCBF are mainly due to physiological and physical factors, the data processing, normalization and co-registration methods. In order to further improve mapping of rCBF with SPET it is imperative not only to improve the spatial resolution but also to apply accurate correction techniques for scatter, attenuation and non-linear extraction. Received 3 August and in revised form 1 October 1997     

Demonstration of decreased posterior cingulate perfusion in mild Alzheimer's disease by means of H2 15O positron emission tomography

Although decreased posterior cingulate metabolism in Alzheimer's disease (AD) has been previously reported, there have been no reports on posterior cingulate perfusion. In this study we evaluated posterior cingulate perfusion as a relative value using statistical parametric maps (SPMs) and as an absolute value using conventional region of interest (ROI) settings. Twenty-eight subjects, including 14 patients with mild AD (mean age: 66.4±12.1 years) and 14 normal controls (65.9±7.3 years) were studied. Regional Cerebral blood flow (CBF) was measured with H₂ ¹⁵O and positron emission tomography (PET). In the SPM analysis, the left posterior cingulate and left parietotemporal CBFs were significantly decreased in the patients with mild AD (P<0.001). At a louver statistical threshold (P<0.05), the right posterior cingulate and right parietotemporal CBFs were also significantly decreased in the AD patients. In the ROI studies, the left parietal and posterior cingulate CBFs in the patients with mild AD were significantly lower than those of the normal controls by analysis of variance and post-hoc Scheffé's test (P<0.001). We conclude that posterior cingulate perfusion is decreased in mild AD, reflecting the pathological changes and metabolic reduction in the posterior cingulate gyrus that have previously been reported to occur in mild AD.     

A diagnostic method for suspected Alzheimer's disease using H2 15O positron emission tomography perfusion Z score

We developed cerebral perfusion Z score map (Z map) images using H₂ ¹⁵O and positron emission tomography (PET), and examined their use in diagnosing Alzheimer's disease (AD). Cerebral blood flow (CBF) images were obtained using the PET and H₂ ¹⁵O autoradiographic method. The best region for normalising the CBF value to remove individual variantion was determined. Then CBF images were transformed to Talairach's standard space, and each pixel value of an individual's image set was normalized to the mean value of the sensorimotor area. Based on the CBF images of 20 normal volunteers, normative mean and standard deviation (SD) CBF images were constructed. Then, each pixel value of the axial CBF images in 28 patients with probable AD and 10 further normal volunteers was converted to a Z score (Z = [normal mean – individual value]/normal SD). A Z map, showing pixels exceeding a threshold of Z score > 2 on MRI of standardised anatomical space was demonstrated. These 38 Z maps were interpreted by four radiologists. When regions in the temporoparietal area were found with Z scores > 2, the subject was diagnosed as having AD. A receiver operating characteristic (ROC) analysis was performed to compare the conventional CBF images and Z maps. The diagnostic performance of the Z map was superior to that of visual inspection of conventional CBF images (mean areas under the ROC curve of the four radiologists were 0.946 and 0.584, respectively). These results indicate that a Z map obtained in this way is superior to conventional PET for diagnosing AD. Received: 13 December 1999 Accepted: 17 March 2000     

Rapid detection of human infections with fluorine-18 fluorodeoxyglucose and positron emission tomography: preliminary results

The purpose of this study was to evaluate the feasibility of 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) and positron emission tomography (PET) for rapid detection of human infections. Eleven patients who were known or suspected to be harboring various infections were studied with FDG-PET. Dynamic scans over the putative infection sites were performed immediately after FDG (370 MBq) injection through 60 min, and static images including multiple projection images were then obtained. FDG uptake was assessed visually into four grades (0, normal; 1, probably normal; 2, probably abnormal; 3, definitely abnormal). For the semiquantitative index of FDG uptake in infections, the standardized uptake value of FDG normalized to the predicted lean body mass (SUV-lean, SUL) was determined from the images obtained at 50–60 min after FDG injection. PET results were compared with final clinical diagnoses. Eleven lesions in eight patients, which were interpreted as grade 2 or 3 by FDG-PET, were all concordant with active infectious foci. The SUL values of infections ranged from 0.97 to 6.69. In two patients, FDG-PET correctly showed no active infection. In one patient, it was difficult to detect infectious foci by FDG-PET due to substantial normal background uptake of FDG. In total, FDG-PET correctly diagnosed the presence or absence of active infection in 10 of 11 patients. Fusion images of PET with computed tomography showed the most intense FDG uptake to be within an abscess wall. In conclusion, FDG-PET appears to be a promising modality for rapid imaging of active human infections. More extensive clinical evaluation is warranted to determine the accuracy of this method. Received 5 March and in revised form 20 May 1998     

Measurement of cerebral blood flow with a bolus of oxygen-15-labelled water: Comparison of dynamic and integral methods

A method is presented for the measurement of cerebral blood flow (CBF) with a bolus of water labelled with oxygen 15. The method, which has been evaluated in normal volunteers, is based on Kety's model, with two additional parameters to account for the difference in the time of tracer arrival in the radial and carotid arteries (delay) and for dispersion of the tracer in the body and/or blood counting systems. It combines the advantages of: (i) dynamic data collection for estimation of delay and dispersion; (ii) robustness and linearity of CBF estimates with an integral method; and (iii) simplicity of continuous external monitoring of arterial blood radioactivity, particularly with repeated measurements. An optimized protocol is proposed for routine applications in neurological and neurophysiological studies.     

Regional cerebral glucose consumption measured by positron emission tomography in patients with Wilson's disease

Using positron emission tomography (PET), the regional cerebral metabolic rate of glucose consumption (rCMRGlc) was measured in 14 patients with Wilson's disease (WD) and 23 normal subjects. In WD patients, cerebellar, striatal and — to a lesser extent — cortical and thalamic rCMRGIc were significantly decreased compared with controls. Striatal rCMRGIc was significantly reduced in those 4 patients who had recently started decoppering therapy as compared with striatal rCMRGlc measured in those 10 patients with longer duration of medication. Caudate rCMRGlc correlated significantly with various signs of extrapyramidal dysfunction. Cerebellar, thalamic and cortical rCMRGlc correlated significantly with the severity of pyramidal signs. These data indicate that the PET measurement of rCMRGIc may be a useful tool to evaluate cerebral involvement in WD and to monitor the response to treatment. Offprint requests to: T. Kuwert     

Blood flow and blood volume in the femoral head of healthy adults according to age: Measurement with positron emission tomography (PET)

OBJECTIVE: To deepen understanding of hemodynamics in the femoral head, i.e., the essential factor in clarifying pathogenesis of hip disorders, this study examined blood flow and blood volume in the femoral heads of healthy adults, and their changes with age, by using positron emission tomography (PET). METHODS: In 16 healthy adult males (age: 20-78 years old, mean age: 42 years), blood flow was measured by means of the H2(15)O dynamic study method, and blood volume was measured by means of the (15)O-labeled carbon monoxide bolus inhalation method. RESULTS: Blood flow was 1.68-6.47 ml/min/100 g (mean +/- SD: 3.52 +/- 1.2), and blood volume was 1.67-6.03 ml/100 g (mean +/- SD: 3.00 +/- 1.27). Blood flow significantly decreased (p < 0.01) with age, and blood volume significantly increased (p < 0.05). CONCLUSION: PET was useful in the measurement of blood flow and blood volume in the femoral heads. With age, physiological hemodynamic changes also increased in femoral heads.     

Cerebral oxygen and glucose metabolism and blood flow in mitochondrial encephalomyopathy: a PET study

Cerebral blood flow (CBF), oxygen metabolism (CMRO₂), and glucose metabolism (CMRGlc) were measure using positron emission tomography in five patients diagnosed as having mitochondrial encephalomyopathy. The molar ratio between the oxygen and glucose consumptions was reduced diffusely, as CMRO₂ was markedly decreased and CMRGlc was slightly reduced. The CBF showed less changes. The CBF increase on hypercapnia was smaller than normal, though this was not significant. CBF with hypocapnia demonstrated a significant reduction compared with the normal. These results suggest that oxidative metabolism is imparied and anaerobic glycolysis relatively stimulated, due to a primary defect of mitochondrial function, and that mild lactic acidosis occurs in brain tissue because of impaired utilisation of pyruvate in the TCA cycle. As these findings appear to indicate directly a characteristic of this disease, such measurements may be a useful tool for assessment of the pathophysiology and for diagnosis of mitochondrial encephalomyopathy.