Effect of exercise induced hyperlactatemia on the biodistribution and metabolism of iodine-123-15(p-iodophenyl)-3-R,S-methyl pentadecanoic acid in normal volunteers

We have evaluated the biodistribution and metabolism of iodine-123-15-(p-iodophenyl)-3-R,S-methyl pentadecanoic acid (BMIPP) in the presence of increased lactate levels induced by short-term heavy exercise. Five healthy male subjects received 159 MBq (+/- 13 MBq) 123I-BMIPP at rest and a week later after they performed a maximal exercise test using a bicycle ergometer. Planar and tomographic images were obtained with a dual-head gamma camera up to 4 h after administration of the tracer. Multiple blood samples were taken at different time points for blood clearance, substrate concentration measurements and for HPLC analysis of metabolites. The exercise test did not alter plasma glucose and non-esterified fatty acid concentrations, but blood lactate increased from 1.12 mmol/l at rest to 9.26 mmol/l with maximal exercise. After exercise, BMIPP showed a significantly faster plasma clearance than at rest and the production of PIPA, the end metabolite of BMIPP oxidation, was reduced. Activity in the heart was similar after exercise and at rest on planar images 15 min after injection (4.83 +/- 0.50% ID vs 4.80 +/- 0.43% ID, P = NS), although the myocardium-to-cavity activity ratio, as determined on the SPET images 20 min after tracer injection, was slightly increased after the exercise test (4.20 +/- 0.63 vs 3.78 +/- 1.34 at rest, P = NS). Significantly increased activity was observed in a leg muscle region of interest after exercise (4.98 +/- 0.50% ID vs 3.93 +/- 0.44% ID at rest, P = 0.02). Between early and late images, tracer washout from the myocardium increased from 20.72% at rest to 36.72% after exercise (P < 0.05), but was unchanged for liver and leg muscles. The metabolic and physiological alterations induced by exercise do not degrade image quality of BMIPP scintigraphy. On the contrary, exercise-induced hyperlactatemia seems to enhance myocardium-to-cavity activity ratios on SPET images, although this effect does not reach statistical significance in this small group of normal subjects. These findings further support the robustness of BMIPP SPET in varied metabolic environments.     

Evaluation of radiotherapeutic response in non-small cell lung cancer patients by technetium-99m MIBT and thallium-201 chloride SPET

The purpose of this study was to investigate the relationship between technetium-99m hexakis-2-methoxyisobutylisonitrile (^99mTc-MIBI) accumulation in tumours and response to radiotherapy in non-small cell lung cancer patients in comparison with the findings obtained using thallium-201 chloride (²⁰¹Tl).Simultaneous dual single-photon emission tomography (SPET) imaging with 600 MBq ^99mTc-MIBI and 111 MBq ²⁰¹Tl was performed in 31 patients with biopsy- or sputum cytology-proven lung cancer. SPET images were acquired 15 min (early) and 2 h (delayed) after injection, and the early ratio, delayed ratio and retention index were measured. The tumours were classified into two groups on the basis of follow-up computed tomography (CT): responders (at least 50% reduction in tumour size) and non-responders (little or no change in tumour size).The mean (± SD) values of early ratio, delayed ratio and retention index using ^99mTc-MIBI SPET were 3.0±1.1, 2.7±1.0 and –9.5±12.7, respectively, in responders and 2.4±0.7, 2.0±0.5 and –18.4±9.0, respectively, in non-responders. The corresponding values using ²⁰¹Tl chloride SPET were 3.7±1.0, 4.7±1.5 and 24.2±22.1 in responders and 3.3±1.2, 4.0±1.3 and 20.4±20.5 in non-responders. Using ^99mTc-MIBI, the delayed ratio and retention index in responders were significantly higher than those in non-responders (P<0.01 and P<0.05, respectively). The results of this study indicate that patients with higher delayed ratio and retention index values using ^99mTc-MIBI SPET are likely to respond better to radiotherapy than those with lower values. ^99mTc-MIBI SPET may give an indication of the short-term response to radiotherapy in patients with non-small cell lung cancer. Received 1 November 1999 and in revised form 8 January 2000     

Influence of exercise rehabilitation on myocardial perfusion and sympathetic heart innervation in ischaemic heart disease

Exercise rehabilitation improves the clinical status in ischaemic heart disease. The purpose of this study was to assess the influence of exercise rehabilitation on myocardial perfusion and sympathetic heart innervation. Sixteen patients with ischaemic heart disease and previous myocardial infarction were investigated by means of exercise/rest tetrofosmin and metaiodobenzylguanidine (MIBG) exercise/rest single-photon emission tomography (SPET) studies, before and 6 months after starting an exercise rehabilitation programme. Tomograms were divided into 15 segments, and these were grouped into five myocardial anatomical regions. Regional uptake of both tracerswas quantified and expressed as a percentage of maximumpeak activity. The percentage ≤55% was chosen to evaluate defect size, and the results were expressed as a percentage of left ventricular mass. Areas with perfused and denervated myocardium and areas with ischaemic myocardium were calculated. In addition, regions with <75% of peak activity in the exercise perfusion study at baseline were divided into two groups according to whether there was an increase in peak activity of >10% (representing reversible regional defects) or an increase of <10% (representing fixed regional defects) in the rest study. These percentages were compared with the percentages obtained in the innervation study, and with the percentages obtained in exercise/rest perfusion and innervation studies performed 6 months after starting rehabilitation. Myocardial perfusion defects were significantly smaller than myocardial innervation defects before and 6 months after starting exercise rehabilitation. The area of ischaemia 6 months after starting exercise rehabilitation was significantly smaller than that before rehabilitation (0.31%± 1.4% vs 1.4%±1.6%, P<0.01). The size of innervation defects and the area of perfused and denervated myocardium did not show significant differences between the two studies performed before and 6 months after starting exercise rehabilitation. In reversible regional defects the percentage of peak activity was significantly increased 6 months after starting exercise rehabilitation in exercise and rest studies (P<0.001), while in fixed regional defects it was significantly increased only in exercise studies (P<0.001). There was no significant change in the regional MIBG percentages. We conclude that in ischaemic heart disease, exercise rehabilitation over a period of 6 months improves myocardial perfusion, but does not cause changes in sympathetic myocardial innervation. Received 12 August and in revised form 17 November 1999     

Clinical evaluation of no-carrier-added meta-[123I]iodobenzylguanidine for myocardial scintigraphy

In clinical and research studies, images obtained using carrier-added meta-[¹²³I]iodobenzylguanidine (c.a. [¹²³I]MIBG) have shown quite variable quality, with varying levels of uptake in lung, liver and mediastinum; this is a significant problem for quantification of the myocardial uptake by means of region ratios. First experimental and preliminary human data in respect of no-carrier-added (n.c.a.) [¹²³I]MIBG are indicative of improved imaging quality. The aim of the present study was to evaluate the clinical value of myocardial scintigraphy with n.c.a. [¹²³I]MIBG in patients with tachyarrhythmias. The study population comprised 24 patients with tachyarrhythmogenic diseases routinely studied by cardiac single-photon emission tomography (SPET) with [¹²³I]MIBG. Twelve of the 24 patients were studied with c.a. [¹²³I]MIBG (seven females and five males; mean age 42±13 years, range 20–60 years), whereas the other 12 were studied with n.c.a. [¹²³I]MIBG (ten females, two males; mean age 41±11 years, range 18–60 years, P=NS). For quantification of the specific uptake in the different organs, count ratios were calculated on SPET images acquired 4 h p.i. Visual analysis of all [¹²³I]MIBG scans showed improved image quality (improved contrast between heart and neighbouring organs) in n.c.a. studies as compared with c.a. studies. A significantly higher heart/left atrial blood ratio was found in the n.c.a. studies as compared with the c.a. studies (10.3±3.2 vs 5.3±1.3, P=0.0003); furthermore, significantly higher heart/lung and heart/liver ratios (2.5±0.6 vs 1.5±0.3, P=0.0002, and 0.8±0.2 vs 0.6±0.1, P=0.0006, respectively) were obtained in the c.a. studies, whereas lung/left atrial blood and liver/left atrial blood ratios showed no significant differences (4.2±1.3 vs 3.6±1.1, P=0.39, and 13.7±5.2 vs 9.6±2.2, P=0.21, respectively). In conclusion, the use of n.c.a. [¹²³I]MIBG yields a significantly higher myocardial uptake associated with improvement in contrast between the heart and neighbouring organs and is therefore superior to the commercially available c.a. [¹²³I]MIBG for use in clinical and research studies of the myocardial presynaptic sympathetic nervous system. Furthermore, our data indicate that for quantification the use of a left atrial blood reference region of interest, which is only available on SPET studies, is to be recommended. Received 22 September and in revised form 2 November 1999     

Change in regional pulmonary perfusion as a result of posture and lung volume assessed using technetium-99m macroaggregated albumin single-photon emission tomography

The purpose of this study was to evaluate the effects of gravity and lung volume on regional pulmonary perfusion using technetium-99m macroaggregated albumin (^99mTc MAA) single-photon emission tomography (SPET). Twenty-five subjects were classified into three groups according to their position during the injection of the tracer [11 subjects sitting, six supine and eight both supine and prone (S+P) positions]. All of these subjects were injected with the tracer during normal tidal breathing. In the S+P group, half of the tracer was injected while the subject was in each position. The remaining 11 subjects were classified into two groups according to their lung volume during the injection. Supine patients were instructed to hold their breath at residual volume (RV) (five subjects) or total lung capacity (TLC) (six subjects) while receiving the tracer injection. A region of interest with a ventrodorsal axis was defined in the centre of each lung. Profile curves were produced by plotting and normalizing the perfusion values as a percentage of the maximum value. The perfusion distributions for the sitting and S+P positions and at RV were relatively uniform. However, the distributions for the supine position and at TLC showed a gravitational influence [sitting vs TLC: 87.8%±10.4% vs 67.3%±8.7% for % maximum perfusion at +5 pixels from the midpoint of the upper lobe (P<0.00002)]. The gravity-related perfusion inhomogeneity was more prominent in the lower lobe than in the upper lobe. It is concluded that the physiological vertical gravitational gradient should be taken into consideration during the interpretation of lung SPET images. Preferably, patients should be injected with the tracer twice, once in the supine position and once in the prone position, while breathing normally. Alternatively, they may be injected with the tracer once while in the supine position and holding their breath at RV. Either of these protocols should ensure a uniform distribution of tracer. Received 4 November 1999 and in revised form 18 January 2000     

Limited performance of quantitative assessment of myocardial function by thallium-201 gated myocardial single-photon emission tomography

We investigated the reproducibility between thallium-201 and technetium-99m methoxyisobutylisonitrile (MIBI) gated single-photon emission tomography (SPET) for the assessment of indices of myocardial function such as end-diastolic and end-systolic volume (EDV, ESV), ejection fraction (EF) and wall motion. Rest ²⁰¹Tl (111 MBq) gated SPET was sequentially performed twice in 20 patients. Rest ²⁰¹Tl gated SPET and rest ^99mTc-MIBI (370 MBq) gated SPET were performed 24 h apart in 40 patients. Wall motion was graded using the surface display of the Cedars quantitative gated SPET (QGS) software. EDV, ESV and EF were also measured using the QGS software. The reproducibility of functional assessment on rest ²⁰¹Tl gated SPET was compared with that on ^99mTc-MIBI gated SPET, and also with that between ²⁰¹Tl gated SPET and ^99mTc-MIBI gated SPET performed on the next day. The two standard deviation (2 SD) values for EDV, ESV and EF on the Bland-Altman plot were 29 ml, 19 ml and 12%, respectively, on repeated ²⁰¹Tl gated SPET, compared with 14 ml, 11 ml and 5.3% on repeated ^99mTc-MIBI gated SPET. The correlations were good (r=0.96, 0.97 and 0.87) between the two measurements of EDV, ESV and EF on repeated rest studies with ²⁰¹Tl and ^99mTc-MIBI gated SPET. However, Bland-Altman analysis revealed that the 2 SD values between the two measurements were 31 ml, 23 ml and 12%. We were able to score the wall motion in all cases using the 3D surface display of the QGS on ²⁰¹Tl gated SPET. The kappa value of the wall motion grade on the repeated ²⁰¹Tl study was 0.35, while that of the wall motion grade on the repeated ^99mTc-MIBI study was 0.76. The kappa value was 0.49 for grading of wall motion on repeated rest studies with ²⁰¹Tl and ^99mTc-MIBI. In conclusion, QGS helped determine EDV, ESV, EF and wall motion on ²⁰¹Tl gated SPET. Because the EDV, ESV and EF were less reproducible on repeated ²⁰¹Tl gated SPET or on ²⁰¹Tl gated SPET and ^99mTc-MIBI gated SPET on the next day than on repeated ^99mTc-MIBI gated SPET, functional measurement on ²⁰¹Tl gated SPET did not seem to be interchangeable with that on ^99mTc-MIBI gated SPET. Received 18 May 1999 and in revised form 4 October 1999     

Relation between exercise-induced ventricular arrhythmias and myocardial perfusion abnormalities in patients with intermediate pretest probability of coronary artery disease

The significance of exercise-induced ventricular arrhythmias (VAs) is largely dependent on the clinical characteristics of the studied population. The relation between exercise-induced VAs and myocardial perfusion abnormalities has not yet been evaluated in a homogeneous patient population with intermediate probability of coronary artery disease (CAD). We studied 302 patients (mean age 54±9 years, 152 men and 150 women) with intermediate pretest probability of CAD (range=0.25– 0.80, mean=0.43±0.20) by upright bicycle exercise stress test in conjunction with technetium-99m single-photon emission tomography (SPET) imaging. Exercise-induced VAs (frequent or complex premature ventricular contractions or ventricular tachycardia) occurred in 65 patients (22%). No significant difference was found between patients with and patient without VAs regarding the pretest probability of CAD (0.45±0.21 vs 0.43±0.20). Patients with exercise-induced VAs had a higher prevalence of perfusion abnormalities (52% vs 26%, P=0.002) and ischaemic electrocardiographic changes (31% vs 16%, P<0.05) compared to patients without VAs. A higher prevalence of perfusion abnormalities in patients with VAs was observed in both men (67% vs 35%, P<0.01) and women (38% vs 16%, P<0.05). However, the positive predictive value of exercise-induced VAs for the presence of myocardial perfusion abnormalities was higher in men than in women (67% vs 38%, P<0.05). The presence of abnormal myocardial perfusion was the only independent predictor of exercise-induced VAs (OR 2.2; 95% CI, 1.2–4.2) by multivariate analysis of clinical and stress test variables. It is concluded that in patients with intermediate pretest probability of CAD, exercise-induced VAs are predictive of a higher prevalence of myocardial perfusion abnormalities in both men and women. However, the positive predictive value of exercise-induced VAs for perfusion abnormalities is higher in men. Because of the underestimation of ischaemia by electrocardiographic changes, exercise-induced VAs should be interpreted as a marker of a higher probability of CAD. Received 15 September and in revised form 27 October 1999     

Exercise-induced stunning continues for at least one hour: evaluation with quantitative gated single-photon emission tomography

To elucidate the after-effect of exercise on left ventricular (LV) function, end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (LVEF) were evaluated at 1 h after exercise and at rest by technetium-99m tetrofosmin gated myocardial single-photon emission tomography (SPET) using an automated program in 53 subjects. The subjects were grouped as follows: normal scan (n = 16), ischaemia (n = 19) and infarction (n = 18), based on the interpretation of perfusion images. Postexercise LVEF did not differ from resting LVEF in the groups with normal scan and infarction. In patients with ischaemia, postexercise EDV (90±17 ml, mean ±SD) and ESV (44±15 ml) were significantly higher than EDV (84±15 ml, P = 0.001) and ESV (36±14 ml, P<0.0005) at rest. LVEF was significantly depressed 1 h after exercise (53%±9% vs 58%±9%, P<0.0001). In ischaemic patients with depressed postexercise LVEF, LVEF difference between rest and postexercise showed a significant correlation with the sum of defect scores, which were reversible from exercise to rest perfusion images (r = 0.92, P<0.0001). These results indicate that exercise-induced LV dysfunction (myocardial stunning) continues for at least 1 h in ischaemic patients and that the extent of LVEF depression is determined by the severity of ischaemia. Received 1 October and in revised form 29 December 1998     

Recovery of impaired left ventricular function in patients with acute myocardial infarction is predicted by the discordance in defect size on123I-BMIPP and201TI SPET images

A discrepancy between myocardial perfusion defect and wall motion abnormalities is frequently found early after coronary reperfusion in patients with acute myocardial infarction. The purpose of this study was to assess recovery of impaired left ventricular function by reference to the discordance in defect size between myocardial fatty acid uptake and myocardial perfusion using combined single-photon emission tomographic (SPET) imaging early after coronary perfusion therapy. In 37 patients with acute myocardial infarction, iodine-123 15(p-iodophenyl)-3(R, S)-methylpentadecanoic acid (BMIPP) and thallium-201 SPET scans were performed early after coronary reperfusion. A severity score was determined from the extent of the imaging defect with each tracer. Left ventricular wall motion score (WMS) and ejection fraction (EF) were obtained at admission and at 4 weeks after the onset of infarction. In 32 of the 37 patients, discordance in defect sizes delineated with the two SPET studies was found during the acute stage. The severity score for BMIPP was larger than that for²⁰¹Tl during the acute stage (7.7±2.4 vs 4.4±2.5,P <0.001). There was a fair correlation between the severity score for BMIPP and WMS (r=0.82,P <0.0001), but a poor correlation between that for²⁰¹Tl and WMS. The extent of discordance in severity scores between BMIPP and²⁰¹Tl during the acute stage correlated well with the extent of the improvement in WMS (r=0.86,P <0.0001) and that of EF (r=0.85,P <0.0001). We conclude that the discordance in defect size on BMIPP and²⁰¹TI SPET images during the acute stage of infarction is an early predictor of the viability of the myocardium at risk of infarction.     

Iterative reconstruction: an improvement of technetium-99m MIBI SPET for the detection of parathyroid adenomas?

The purpose of this study was to assess the value of technetium-99m methoxyisobutylisonitrile (MIBI) single-photon emission tomography (SPET) and an iterative reconstruction algorithm for the preoperative localisation of parathyroid adenomas (PTAs). Seventy-two patients (26 male, 46 female, mean age 58±16 years) with known primary hyperparathyroidism were examined preoperatively. First, a thyroid examination was performed to detect possible MIBI-accumulating thyroid lesions. Planar scans were then acquired 15 and 120 min and tomographic images 120 min after intravenous injection of 740 MBq ^99mTc-MIBI, using a triple-head gamma camera (Picker Prism 3000). Additionally, ^99mTc-MIBI/ ^99mTc-pertechnetate subtraction scintigraphy of the early planar images was performed. The SPET data were evaluated using an iterative reconstruction (multiplicative iterative SPET reconstruction: MISR) as well as a standard algorithm (FBP: filtered back-projection with application of a 3-D low-pass postfilter). The weight of the resected PTAs ranged from 110 mg to 5 g. Using planar MIBI scans, correct localisation of the side of the PTA was possible in 81% of cases (58% for PTAs weighing less than 500 mg). Sensitivity increased to 94% using SPET and FBP, while with MISR it rose further, to 97%. Patients with PTAs weighing less than 500 mg showed a sensitivity of 88% with MISR and 81% with FBP. Furthermore, there was a clear improvement in image quality using MISR. None of the normal parathyroid glands were visualised. This study indicates that, in comparison with planar scintigraphy, ^99mTc-MIBI SPET is a more sensitive and specific tool for topographical localisation of PTAs, especially those that are small. There is a further improvement in sensitivity and image quality when iterative reconstruction is used instead of FBP. Received 8 August 1999 and in revised form 20 January 2000     

Low-dose dobutamine gated single-photon emission tomography: comparison with stress echocardiography

Perfusion scintigraphy provides important information regarding the presence of viable tissue after myocardial infarction. Defects of moderate severity, however, may represent viable myocardium, necrotic tissue or a mixture of both. In this study the presence or absence of inotropic response in the infarcted area was assessed by low-dose dobutamine tetrofosmin gated single-photon emission tomography (LDD gated SPET). Results were compared with those obtained with stress echocardiography (SE). Twenty-five patients with acute myocardial infarction were studied. Gated SPET myocardial perfusion imaging was performed 60 min after the injection of technetium-99m tetrofosmin (925 MBq) at rest using a triple-headed camera equipped with focussing collimators (Cardiofocal). Two consecutive acquisitions were performed according to a ”fast” gated SPET protocol (3×20 stops, 9 s/stop, 64×64 pixel matrix, zoom 1.23) with the subjects remaining in the same position. The first acquisition was obtained at rest; the second acquisition was obtained under infusion of 10 μg kg^–1 min^–1 dobutamine. The severity of regional dysfunction, wall thickening severity (WT_sev), was assessed and quantified using a method based on circumferential profile analysis. SE was performed at rest and during infusion of 5 and 10 μg kg^–1 min^–1 dobutamine. Two patients could not be analysed because of disturbing gastro-intestinal activity on the perfusion study. Under dobutamine 11 patients presented a significant change in WT_sev (three showed normalisation, five an improvement and three a deterioration), while in 12 patients the WT_sev score remained unchanged. The overall concordance between LDD gated SPET and SE was 83%. In patients with perfusion defects of moderate severity the concordance was 90% (9/10). It may be concluded that functional changes in infarcted areas induced by dobutamine can be detected with gated SPET. Good agreement was observed between LDD gated SPET and SE for the identification of inotropic reserve in infarcted areas. Received 5 September and in revised form 22 November 1999     

Scintigraphic detection of acute experimental endocarditis with the technetium-99m labelled glycoprotein IIb/IIIa receptor antagonist DMP444

Bacterial endocarditis is an important clinical problem that may result in persistent bacteraemia and irreversible cardiac damage. Since endocarditis is characterized by aggregation of activated platelets, fibrin and bacteria, we studied DMP444, a technetium-99m labelled high-affinity antagonist of the GP IIb/IIIa receptor that is expressed on activated platelets. In seven Beagle dogs (11–15 kg), the left ventricle was catheterized via the right carotid artery. One hour later, 5×10⁷ colony forming units of Staphylococcus aureus were injected intracardially. Half an hour later, the catheter was removed. Two extra dogs underwent a complete sham procedure. One day after the intervention, five infected and the two non-infected dogs were injected with 37 MBq/kg ^99mTc-DMP444 and two infected dogs with 37 MBq/kg ^99mTc-IgG (used as a non-specific control agent) and imaged up to 4 h after injection. Samples were obtained for tissue counting, microbiology and histology. From 1 to 2 h post injection onward, there was clear focal accumulation of DMP444 in the aortic valve region when endocarditis was present, and this accumulation increased with time. The non-infected and the ^99mTc-IgG injected dogs showed only persisting blood pool activity without any focal abnormality. At 4 h post injection, the in vivo valve-to-blood pool ratios were 1.87±0.18 in endocarditis, 1.01±0.05 in non-infected controls and 1.09±0.02 in ^99mTc-IgG injected dogs (P<0.05). It is concluded that targeting activated platelets with the ^99mTc-labelled GP IIb/IIIa antagonist DMP444 allows a final diagnosis of experimental bacterial endocarditis within 4 h owing to high, specific and fast in vivo uptake. Received 6 October and in revised form 27 December 1999     

Peripheral sympathetic dysfunction in patients with Parkinson’s disease without autonomic failure is heart selective and disease specific

The study was undertaken to investigate by means of iodine-123-labelled metaiodobenzylguanidine (MIBG) scintigraphy the peripheral sympathetic function in patients with Parkinson’s disease (PD) without autonomic failure and in patients with related neurodegenerative diseases with parkinsonism. Seventy patients (33 men and 37 women, mean age 63±9.7 years) with parkinsonism and ten control subjects underwent MIBG scintigraphy. Of these 70 patients, 41 were diagnosed as having idiopathic PD, 9 multiple system atrophy (MSA), 6 progressive supranuclear palsy (PSP) and 2 corticobasal degeneration (CBD); the remaining 12 were diagnosed as having neurodegenerative disease with parkinsonism (P-nism) that did not meet the diagnostic criteria of any specific disease. Cardiac planar and tomographic imaging studies and subsequent whole-body imaging were performed 20 min and 3 h after the injection of 111 MBq MIBG. The early MIBG heart to mediastinum (H/M) ratio in PD (1.61±0.29) was significantly lower than that in the control group (2.24±0.14, P<0.01), P-nism (2.15±0.31, P<0.01), MSA (2.08±0.31, P<0.05) and PSP (2.30±0.24, P<0.01). The delayed H/M ratio in PD (1.47±0.34) was also significantly lower than that in the control group (2.37±0.14, P<0.01), P-nism (2.13±0.38, P<0.01), PSP (2.36±0.36, P<0.01) and MSA (2.17±0.36, P<0.01). In patients with PD, early and delayed H/M ratios were significantly decreased in disease stages I, II and III (established using the Hoehn and Yahr criteria) as compared with control subjects, and there were no significant differences among the stages. Only PD showed a significantly higher washout rate (WR) than that in the control subjects (27%±8.0% vs 11%±4.2%, P<0.01). Early and delayed uptake ratios of the lung, parotid gland, thyroid gland, liver and femoral muscles in each of the patient groups were not significantly different from those in control subjects. Only the early and delayed uptake ratios of the lower leg muscles in MSA were significantly lower than those in the control group (P<0.05). In conclusion: In patients with PD without autonomic failure, only cardiac MIBG uptake was severely reduced in the earliest phase of the disease (stage I). Parkinsonian syndromes other than PD did not demonstrate significant reduction in MIBG uptake in any organs except for the lower legs in MSA. In patients with PD without autonomic failure, reduction in MIBG uptake occurs selectively in the heart; this is considered to be a specific finding for PD and useful for the differential diagnosis of the parkinsonian syndromes. Received 13 September and in revised form 29 December 1999     

Non-invasive estimation of myocardial efficiency using positron emission tomography and carbon-11 acetate – comparison between the normal and failing human heart

The clearance kinetics of carbon-11 acetate, assessed by positron emission tomography (PET),can be combined with measurements of ventricular function for non-invasive estimation of myocardial oxygen consumption and efficiency. In the present study, this approach was applied to gain further insights into alterations in the failing heart by comparison with results obtained in normals. We studied ten patients with idiopathic dilated cardiomyopathy (DCM) and 11 healthy normals by dynamic PET with ¹¹C-acetate and either tomographic radionuclide ventriculography or cine magnetic resonance imaging. A ”stroke work index” (SWI) was calculated by: SWI = systolic blood pressure × stroke volume/body surface area. To estimate myocardial efficiency, a ”work-metabolic index” (WMI) was then obtained as follows: WMI = SWI × heart rate/k(mono), where k(mono) is the washout constant for ¹¹C-acetate derived from mono-exponential fitting. In DCM patients, left ventricular ejection fraction was 19%±10% and end-diastolic volume was 92±28 ml/m² (vs 64%±7% and 55±8 ml/m² in normals, P<0.001). Myocardial oxidative metabolism, reflected by k(mono), was significantly lower compared with that in normals (0.040±0.011/min vs 0.060± 0.015/min; P<0.003). The SWI (1674±761 vs 4736± 895 mmHg × ml/m²; P<0.001) and the WMI as an estimate of efficiency (2.98±1.30 vs 6.20±2.25×10⁶ mmHg × ml/m²; P<0.001) were lower in DCM patients, too. Overall, the WMI correlated positively with ejection parameters (r=0.73, P<0.001 for ejection fraction; r=0.93, P<0.001 for stroke volume), and inversely with systemic vascular resistance (r=–0.77; P<0.001). There was a weak positive correlation between WMI and end-diastolic volume in normals (r=0.45; P=0.17), while in DCM patients, a non-significant negative correlation coefficient (r=–0.21; P=0.57) was obtained. In conclusion non-invasive estimates of oxygen consumption and efficiency in the failing heart were reduced compared with those in normals. Estimates of efficiency increased with increasing contractile performance, and decreased with increasing ventricular afterload. In contrast to normals, the failing heart was not able to respond with an increase in efficiency to increasing ventricular volume. The present data support the usefulness of the WMI for non-invasive characterization of cardiac efficiency and may serve as a background for improved evaluation of medical therapy for heart failure. Received 10 August and in revised form 3 November 1999     

Transmission imaging for registration of ictal and interictal single-photon emission tomography, magnetic resonance imaging and electroencephalography

A method developed for registration of ictal and interictal single-photon emission tomography (SPET), magnetic resonance imaging (MRI) and electroencephalography (EEG) is described. For SPET studies, technetium-99m ethyl cysteinate dimer (ECD) was injected intravenously while the patient was monitored on video-EEG to document the ictal or interictal state. Imaging was performed using a triple-head gamma camera equipped with a transmission imaging device using a gadolinium-153 source. The images (128×128 pixels, voxel size 3.7×3.7×3.6 mm³) were reconstructed using an iterative algorithm and postfiltered with a Wiener filter. The gold-plated silver electrodes on the patient’s scalp were utilized as markers for registration of the ictal and interictal SPET images, as these metallic markers were clearly seen on the transmission images. Fitting of the marker sets was based on a non-iterative least squares method. The interictal SPET image was subtracted from the ictal image after scaling. The T1-weighted MPRAGE MR images with voxel size of 1.0×1.0×1.0 mm³ were obtained with a 1.5-T scanner. For registration of MR and subtraction SPET images, the external marker set of the ictal SPET study was fitted to the surface of the head segmented from MR images. The SPET registration was tested with a phantom experiment. Registration of ictal and interictal SPET in five patient studies resulted in a 2-mm RMS residual of the marker sets. The estimated RMS error of registration in the final result combining locations of the electrodes, subtraction SPET and MR images was 3–5 mm. In conclusion, transmission imaging can be utilized for an accurate and easily implemented registration procedure for ictal and interictal SPET, MRI and EEG. Received 20 September and in revised form 16 October 1999     

Therapeutic effect of co-enzyme Q10 on idiopathic dilated cardiomyopathy: assessment by iodine-123 labelled 15-(p-iodophenyl)-3(R, S)-methylpentadecanoic acid myocardial single-photon mission tomography

It has been reported that myocardial mitochondrial function can be improved by the administration of co-enzyme Q10 (CoQ10). Recently, iodine-123 labelled 15-(p-iodophenyl)-3-(R, S)-methylpentadecanoic acid (BMIPP) was developed for metabolic imaging using single-photon emission tomography (SPET). This study was conducted to determine whether the therapeutic effects of CoQ10 on idiopathic dilated cardiomyopathy can be evaluated by BMIPP myocardial SPET. Fifteen patients, comprising 14 men and one woman (mean age: 64±12 years), were examined. CoQ10 was administered at 30 mg/day for a period of 35.7±12.4 days. BMIPP myocardial SPET was carried out belote and after CoQ 10 treatment. The count ratio of the heart (H) to the upper mediastinum (M) (H/M ratio) was calculated using a region of interest method with anterior planar imaging. Representative short-axis tomograms were divided into 27 segments (three slicesxnine segments). Each segmental score was analysed semiquantitatively using a four-point scoring system (normal=0, mild low uptake=1, severe low uptake=2, defect=3). The H/M ratio showed a significant improvement., from 2.39±0.39 to 2.54±0.47, after treatment (P<0.05). The BMIPP total defect score after CoQ10 treatment was significantly decreased to 10.1±43, compared to 13.9±4.5 without CoQ10 treatment (P<0.001). However, the percent fractional shortening measured using echocardiography was not significantly different before and alter CoQ treatment (19.2±8.1 vs 19.7±7.1). BMIPP myocardial SPET was confirmed to be sensitive in evaluating the therapeutic effects of CoQ 10 in patients with idiopathic dilated cardiomyopathy. This method is unique, since the therapeutic effects can be estimated from the perspective of metabolic SPET imaging.     

Use of 123I-BMIPP single-photon emission tomography to estimate areas at risk following successful revascularization in patients with acute myocardial infarction

Previous studies have indicated that iodine-123 labelled β-methyliodophenyl pentadecanoic acid (BMIPP), an iodinated fatty acid analogue, can identify persistent alteration of fatty acid metabolism after restoration of blood flow. To assess whether fatty acid imaging can delineate areas at risk following successful revascularization in patients with acute myocardial infarction (AMI), BMIPP findings at 1 week post AMI were compared with perfusion imaging before and after revascularization therapy. Sixty-five patients with AMI underwent technetium-99m tetrofosmin single-photon emission tomography (SPET) before m (TF0) and 1 week (TF1) after successful revascularization therapy. BMIPP SPET was also performed under a fasting state at 1 week (BM1) post AMI. The extent scores were calculated from the defect scores in 20 segments. The BM1 score (7.7±3.9) was similar to the TF0 score (8.8±4.2) (r=0.86, P<0.0001), but significantly higher than the TF1 score (5.8±3.9) (P<0.0001). A significant correlation was observed between the BM1 score and TF0 score (r=0.86, P<0.0001). Among a total of 1300 segments, the BM1 score was identical to the TF0 score in 1156 (88.9%). These data indicate that the ability of BMIPP imaging at 1 week post AMI to identify areas at risk is similar to that of tetrofosmin perfusion imaging in the acute phase. This may be due to the impairment of fatty acid uptake and metabolism reflecting prior severe ischaemic insult which persists at least 1 week after recovery of perfusion in the acute phase of AMI. Received 21 February and in revised form 28 May 1998     

Testicular function after radioiodine therapy for thyroid carcinoma

Radiotherapy can cause infertility in both men and women. However, few data are available concerning the effects of radioiodine therapy for thyroid carcinoma on testicular function. We investigated 25 men (age 23–73 years) with differentiated thyroid carcinoma in a longitudinal prospective trial. Follicle-stimulating hormone (FSH), inhibin B, luteinising hormone (LH) and testosterone were measured before (n=25) and 3 months (n=11), 6 months (n=18), 12 months (n=22), and 18 months (n=18) after radioiodine therapy [radioiodine dose (mean ± SEM): 9.8±0.89 GBq]. Before therapy, FSH was 5.4±0.77 IU/l; it increased significantly (P<0.001) to 21.3±2.4 IU/l after 6 months and fell to 7.4±1.3 IU/l after 18 months (normal range: 1.8– 9.2 IU/l). Inhibin B was significantly decreased (P<0.001) from 178±25.3 pg/ml before therapy to 22.2±5.5 pg/ml after 3 and 29.4±5.7 pg/ml after 6 months and rose to 154±23.3 pg/ml after 18 months (normal range 75– 350 pg/ml). LH and testosterone were within the normal range during the whole study (1.6–9.2 IU/l and 10.4–34.7 nmol/l, respectively). LH was significantly increased (P<0.001) from 2.8±0.33 IU/l before therapy to 5.9±0.69 IU/l 6 months after therapy and then fell slowly to 4.0±0.45 IU/l after 18 months. Total testosterone was significantly increased (P<0.01) from 12.8±0.99 nmol/l at baseline to 19.8±1.7 nmol/l after 12 months and 19.6±1.7 nmol/l after 18 months. The testosterone/LH ratio (normal range: 3.3–17.9 nmol/IU) fell from 5.8±0.66 nmol/IU to 3.0±0.36 nmol/IU after 3 months (P<0.01); it remained close to the latter value after 6 months (3.4±0.49 nmol/IU) and then rose to 5.5± 0.6 nmol/IU after 18 months. In conclusion, 3 and 6 months after radioiodine therapy all patients showed elevated FSH and decreased inhibin B levels, reflecting severely impaired spermatogenesis. At the same time a compensated insufficiency of the Leydig cell function was observed. Eighteen months after the last radioiodine therapy, mean values of gonadal function had completely recovered. Received 5 October and in revised form 27 December 1999     

Role of 123I-IMP SPET in the early diagnosis of borderline chronic hydrocephalus after aneurysmal subarachnoid haemorrhage

Chronic hydrocephalus after aneurysmal subarachnoid haemorrhage (SAH) is easily diagnosed in most cases. However, the diagnosis is sometimes difficult in borderline cases, in which (a) pathognomonic clinical deterioration due to hydrocephalus is masked by the neurological deficits caused in the acute stage of SAH and (b) ventricular enlargement is not so marked on CT scan. The purpose of this study was to investigate whether or not iodine-123 labelled N-isopropyl-p-iodoamphetamine (¹²³I-IMP) single-photon emission tomography (SPET) is of value for the early diagnosis of borderline chronic hydrocephalus after SAH. Fifteen patients who met the criteria of borderline chronic hydrocephalus were selected for the study, and underwent a shunt operation. The patients were divided into a shunt-effective group and a shunt-ineffective group according to neurological improvement after the shunt operation. ¹²³I-IMP SPET was performed in the acute stage of SAH, within 1 week before the shunt operation, and 2 weeks after the shunt operation. Regional cerebral blood flow was estimated by the ¹²³I-IMP autoradiographic method. Pre-shunting periventricular low-perfusion areas showed statistically significant differences between the two groups (P<0.05). In the shunt-effective group, periventricular low-perfusion areas on pre-shunting SPET were significantly enlarged compared with those in the acute stage of SAH (P<0.05), and they were significantly reduced after the shunt operation (P<0.05). In the shunt-ineffective group, periventricular low-perfusion areas showed no significant changes during the course. These results suggest that periventricular low-perfusion areas enlarge in the early stage of chronic hydrocephalus after SAH, and that ¹²³I-IMP SPET can be used for both the early diagnosis of borderline chronic hydrocephalus after SAH and the prediction of shunt effectiveness. Received 21 October and in revised form 27 December 1999     

Improving the cervical spine X-ray in trauma patients utilizing dynamic range compression (DRC) modified digital radiography

Purpose: Inadequate cervical spine X-rays delay diagnosis and treatment and add radiation exposure to trauma patients with suspected cervical spine injury. Digital radiography (DR) with dynamic range compression (DRC) modification can improve the visualization of abnormalities in the cervical spine X-ray. Methods: Two digital hard copy cervical spine X-rays from each of 65 trauma patients were used, both with standard DR processing, and with the second image having the DRC algorithm applied. Blinded readers from emergency medicine, surgery, radiology, and critical care specialties evaluated the films with data analyzed by Student's t-test and ϰ²; P < 0.05. Results: Readers cleared more of the DRC than of the non-DRC images: 41 % vs 30 %, P < 0.001. More vertebral bodies were visualized on DRC than on non-DRC images: 65 % vs 53 % showing C7, P < 0.001. For overall impression of the image quality, DRC images rated higher on a 10-cm visual analog scale than non-DRC: 6.7 vs 4.2, P < 0.001. Conclusions: DRC modification of DR images enabled physicians to evaluate cervical spine X-rays more rapidly and accurately after trauma, requiring fewer repeat films.