Iodine-123-labelled fatty acids for myocardial single-photon emission tomography: current status and future perspectives

Renewed interest in the clinical use of iodine-123-labelled fatty acids is currently primarily focused on the use of iodine-123-labelled 15-(p-iodophenyl)pentadecanoic acid (IPPA) and modified fatty acid analogues such as 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) which show delayed myocardial clearance, thus permitting single-photon emission tomographic imaging. Interest in the use of BMIPP and similar agents results from the differences which have often been observed in various types of heart disease between regional myocardial uptake patterns of [¹²³I]BMIPP and flow tracer distribution. Although the physiological basis is not completely understood, differences between regional fatty acid and flow tracer distribution may reflect alterations in important parameters of metabolism which can be useful for patient management or therapy planning. These tracers may also represent unique metabolic probes for correlation of energy substrate metabolism with regional myocardial viability. The two agents currently most widely used clinically are¹²³I-labelled IPPA and BMIPP. While [¹²³I]IPPA is commercially available as a radiopharmaceutical in Europe (Cygne) and Canada (Nordion), multicenter trials are in progress in the United States as a prelude to approval for broad use. [¹²³I]BMIPP was recently introduced as Cardiodine for commercial distribution in Japan (Nihon Medi-Physics, Inc.). [¹²³I]BMIPP is also being used in clinical studies on an institutional approval basis at several institutions in Europe and the United States. In this review, the development of a variety of radioiodinated fatty acids is discussed. The results of clinical trials with [¹²³I]IPPA and [¹²³I]BMIPP are discussed in detail, as are the future prospects for fatty acid imaging.     

Identification of the central vestibular projections in man: a positron emission tomography activation study

The cerebral representation of space depends on the integration of many different sensory inputs. The vestibular system provides one such input and its dysfunction can cause profound spatial disorientation. Using positron emission tomography (PET), we measured regional cerebral perfusion with various vestibular stimulations to map central vestibular projections and to investigate the cerebral basis of spatial disorientation. We showed that the temporoparietal cortex, the insula, the putamen, and the anterior cingulate cortex are the cerebral projections of the vestibular system in man and that the spatial disorientation caused by unilateral vestibular stimulation is associated with their asymmetric activation.     

Survey on the use of pulmonary scintigraphy, spiral CT and conventional pulmonary angiography for suspected pulmonary embolism in the British Isles

AIM: To determine current clinical practice in the radiological diagnosis of acute pulmonary embolism and assess the use of spiral volumetric computed tomography. METHOD: A survey of 327 acute hospitals including cardiothoracic and orthopaedic tertiary referral centres was undertaken to assess current utilization of lung scintigraphy, spiral computed tomography and pulmonary angiography in the investigation of suspected pulmonary embolism. Responses were received from 215/327 (66%) centres. RESULTS: Lung scintigraphy was provided by 208 hospitals (144 on-site and 64 off-site). Spiral CT services were provided by 111 (52%) hospitals (on- or off-site), 142 (66%) units had access to angiographic facilities. Sixty-three centres out of 215 (29%) offered both on-site lung scintigraphy and spiral CT while only 41/215 (19%) hospitals were able to undertake all three tests on-site. On average, 501 perfusion (Q) or ventilation-perfusion (V/Q) scintigrams were performed per hospital per year with 26 spiral CT studies and just 4.6 pulmonary angiograms. CONCLUSION: These data suggest that lung scintigraphy is frequently the only imaging test in patients other than chest radiography, despite the large number of indeterminate results reported in most series.     

Cerebral bleeding, infarcts, and persumed extrapontine myelinolysis in hypernatraemic dehydration

Abstract The neuroimaging findings in an infant with hypernatremic dehydration are presented. Brain parenchymal haemorrhage and extensive multiple infarcts were present in the acute stage. Follow-up CT showed bilateral, symmetrical changes presumed to indicate extrapontine myelinolysis in the thalamus and globus pallidus. MRI confirmed sparing of the pons. Only three previous cases of neuroimaging abnormalities due to hypernatraemia have been described in the radiological literature. Received: 30 December 1997 Accepted: 6 May 1998     

Non-invasive assessment of skeletal kinetics using fluorine-18 fluoride positron emission tomography: evaluation of image and population-derived arterial input functions

To measure regional skeletal kinetics using fluorine-18 fluoride positron emission tomography (PET) it is necessary to know the concentration of radioactive tracer being delivered to bone by arterial plasma with relation to time, the arterial input function (IFa). Methods by which IFa can be derived without arterial sampling are attractive because of their relative technical simplicity and the reduction in possible morbidity to the subject. We have compared the use of a scaled population input function (IFp) and a corrected image-derived input function from the aorta (IFi) with an IFa directly measured from a radial artery line in ten normal postmenopausal women. Both of the aforementioned methods rely only on a small number of discrete venous samples. Each subject had a dynamic PET acquisition of the lumbar spine performed after the intravenous injection of 180 MBq ¹⁸F-fluoride. Both the IFp and the IFi were compared with the IFa in terms of the accuracy of determination of six parameters. These were: plasma clearance of fluoride to bone mineral (K _i), unidirectional plasma clearance to total bone tissue (K ₁) and individual rate constants k ₂, k ₃ and k ₄, calculated using non-linear regression with a three-compartment model, and the plasma clearance to bone mineral calculated using the Patlak method (K _pat). For both the IFp and the IFi method the root mean square errors for K _pat and K _i were similar and small (<8.2%). The errors in determining K ₁ and the rate constants k ₂ to k ₄ are larger by either method, but with a small advantage using the IFp method. It is concluded that the use of either non-invasive method for determining the arterial plasma input function is suitable for the measurement of the most important parameters, K _i and K _pat, in these subjects. Received 8 April and in revised form 11 July 1999     

Cryptococcus meningoencephalitis in AIDS: parenchymal and meningeal forms

CT and MRI in one case of Cryptococcus neoformans infection showed contrast-enhancing parenchymal lesions resembling granulomata or abscesses. After an initial phase without contrast enhancement, the full extent of the lesions was visible within 2 weeks of presentation. The enhancing masses were assumed to represent intracerebral cryptococcomas. Despite evidence of massive meningeal infection on cerebrospinal fluid (CSF) examination, no radiological signs of meningitis, invasion of the Virchow-Robin spaces or ventriculitis could be demonstrated. With antimycotic treatment the contrast enhancement disappeared and cystic, partly calcified lesions remained. Recurrence of meningeal infection without radiological correlates was apparent in this stage. In a second case of proven cryptococcus meningitis, dilation of Virchow-Robin spaces or cysts in the adjacent parenchyma were the main abnormalities on MRI. Enhancing masses were not detected. These cases may represent two different reactions of the immunocompromised hosts to infection with C. neoformans: widening of the perivascular spaces as a correlate of the more typical meningeal infection and enhancing parenchymal lesions as a sign of further invasion from the CSF spaces. Enhancement of cryptococcomas, indicating an inflammatory response in the surrounding brain, is not typical in patients with impairment of immune function. Received: 11 March 1998 Accepted: 19 June 1998     

Chronic spinal subdural haematoma associated with intracranial subdural haematoma: CT and MRI

Chronic spinal subdural haematoma is a uncommon. We describe the CT and MRI appearances of chronic spinal and intracranial subdural haematomas following minor trauma. The aetiology, pathogenesis and differential diagnosis are discussed. Received: 7 January 1998 Accepted: 15 July 1998     

Effects of sciatic neurectomy on the femur in growing rats: Application of peripheral quantitative computed tomography and Fourier transform infrared spectroscopy

The effects of unilateral sciatic neurectomy (USN) on the development of the femur were studied in 15 growing Wistar-derived rats (age, 5 weeks). The rats were divided into four groups: USN-operated group (right femur), USN-nonoperated group (left femur), sham-operated group (right femur), and sham-nonoperated group (left femur). Bone mineral density (BMD), bone mineral content (BMC), bone area, periosteal circumference, and endosteal circumference were measured by peripheral quantitative computed tomography (pQCT) and the mineral/matrix ratio was evaluated by Fourier transform infrared spectroscopy (FTIR). The USN-operated group showed a significant decrease in cortical BMC, bone area, and periosteal circumference compared with the other groups (P < 0.05). The cortical BMD did not vary significantly between the groups. In the cancellous bone, the USN-operated group showed a significant decrease in BMD and BMC at the metaphysis compared with the other groups (P < 0.05). The mineral/matrix ratio of the cortical bone did not differ significantly between the USN-operated and USN-nonoperated groups. These results suggest that in cortical bone, USN inhibits periosteal bone formation but has no significant effect on the mineral/matrix ratio of cortical bone in femurs. In cancellous bone, USN induces bone loss at the metaphysis. Received: Nov. 19, 1998 / Accepted: Feb. 12, 1999     

Progressive atrophy of the frontal lobes in first-episode schizophrenia: interaction with clinical course and neuroleptic treatment

OBJECTIVE: This prospective study examined the interaction of clinical course of disease and brain structure with time in schizophrenic patients. METHOD: A total of 21 first-episode schizophrenic patients, 10 patients with other psychiatric disorders and a control group of 9 healthy volunteers had CT at first admission and at reinvestigation 5 years later. RESULTS: At first admission all of the patients had enlarged cortical fissures and sulci compared to controls, and the duration of untreated psychosis was significantly correlated with sulcal enlargement. At reinvestigation, frontal and central brain atrophy had progressed in schizophrenic patients. CONCLUSION: The study indicated that ongoing psychosis and lifetime dose of classical antipsychotics were the main candidates accounting for the finding of progressively disturbed brain structure during the first 5 years of schizophrenia.     

Pindolol binding to 5-HT1A receptors in the human brain confirmed with positron emission tomography

The augmentation effect of (–)pindolol as used in combination with SSRI to treat major depression has been ascribed to blocking of dorsal raphe nucleus cell body 5-HT autoreceptors. In this study, the radioligand [carbonyl-¹¹C]WAY-100635 and positron emission tomography were used to establish whether pindolol at a clinical dose level (10 mg s.o.d.) occupies 5-HT_1A receptors in the human brain in vivo. Three healthy males were recruited and each subject was used as his own control. The 5-HT_1A receptor occupancy was calculated for the frontal and temporal cortex and the raphe nuclei, using and a ratio analysis with the cerebellar cortex as the reference region. Maximal pindolol plasma concentration was reached within 3 h after drug administration. Two hours after pindolol administration, the regional 5-HT_1A receptor occupancy was within the range 7–21% in the three subjects. The study confirms that the 5-HT_1A-receptor may be a clinically significant target for pindolol. Received: 8 March 1999 / Final version: 15 March 1999