Markers of bone turnover in Gaucher disease: modeling the evolution of bone disease.

CONTEXT: Gaucher disease (GD) is a lysosomal storage disorder characterized by abundant presence of macrophages. Bone complications and low bone density are believed to arise from enhanced bone resorption mediated through macrophage-derived factors. OBJECTIVE: The objective of the study was to investigate the relationship between bone turnover and bone complications in GD. DESIGN: This was a retrospective cohort study and review of the literature. PATIENTS: Forty adult type I GD patients were included in the study. OUTCOME MEASURES: Levels of the bone-resorption marker, type 1 collagen C-terminal telopeptide, and two bone-formation markers, N-terminal propeptide of type 1 procollagen and osteocalcin, were investigated in relation to clinical bone disease, measures of overall disease severity, and imaging data representing bone marrow infiltration. RESULTS: Osteocalcin was decreased in 50% of our patients (median 0.35 nmol/liter, normal 0.4-4.0), indicating a decrease of bone formation. Type 1 collagen C-terminal telopeptide and N-terminal propeptide of type 1 procollagen were within the normal range for most patients. Osteocalcin concentration was negatively correlated to measures of overall disease severity and positively correlated with imaging data (correlation coefficient 0.423; P = 0.025), suggesting a relation with disease severity. A review of the literature revealed variable outcomes on bone resorption markers but more consistent abnormalities in bone formation markers. Two of three reports conclude that bone-formation parameters increase in response to enzyme therapy, but none describes an effect on bone-resorption markers. CONCLUSIONS: In contrast to earlier hypotheses, we propose that in GD patients, primarily a decrease in bone formation causes an imbalance in bone remodeling.

The clinical value of 18F-FDG detection with a dual-head coincidence camera: a review.

Positron emission tomography (PET) has evolved into a technique that can accurately determine the distribution of positron-emitting radionuclides. The addition of a coincidence detection mode to a standard dual-head detector system has resulted in the option of single-photon and annihilation coincidence detection. This new device for imaging fluorine-18 2-fluoro-2-deoxy-D-glucose (18F-FDG) accumulation in neoplasms became commercially available in 1994. Besides conventional low-energy imaging in the collimated single-photon mode, it offers a relatively inexpensive opportunity to perform uncollimated PET by switching to the coincidence acquisition mode. This review summarises the clinical value of 18F-FDG detection with a dual-head coincidence camera in oncology. The results are compared with the overall results obtained using dedicated PET scanners. With respect to head and neck tumours, 18F-FDG coincidence mode gamma camera imaging (CGI) yields results that are in agreement with those obtained with dedicated PET scanners. With regard to other malignancies, such as lung cancer, lymphoma and brain tumours, data in the literature are too scarce to draw any definite conclusions. In general, the results of 18F-FDG CGI in tumours >15 mm seem to be comparable to those obtained with dedicated PET scanners, whereas in tumours <15 mm, the relative sensitivity of 18F-FDG CGI is approximately 80%. Using attenuation correction, the diagnostic yield of 18F-FDG CGI may increase. However, further clinical investigation is required to definitely establish its value in staging primary disease, therapy monitoring and assessment of tumour recurrence in clinical oncology.

Aspects of fetal thyroid dose following iodine-131 administration during early stages of pregnancy in patients suffering from benign thyroid disorders.

Detrimental effects on the thyroid of the developing fetus as a result of iodine-131 treatment for thyrotoxicosis of the mother in the first trimester of pregnancy are discussed. Dose estimations under typical clinical circumstances yield a fetal thyroid dose of 100- 450 Sv. This dose may increase considerably if the blood concentration of (131)I in the mother remains high. Under such circumstances there may be fetal thyroid dysfunction, which can lead to severe abnormalities.

Aspects of performance assessment of whole body imaging systems.

Regular quality control is one of the cornerstones of nuclear medicine and a prerequisite for adequate diagnostic imaging. Many papers have been published on quality control of planar and tomographic imaging systems. Up to now, however, only minor attention has been given to the assessment of the performance of whole body imaging systems. In this paper we present a comprehensive set of test procedures including acceptance testing and regular quality control. It is not our purpose to present a thorough analysis of the methods and results. The selection of the tests is discussed and the tests are described; some results are presented. In addition action thresholds are proposed. The quality control tests can be applied to systems with either a moving detector or a moving imaging table, and to both detectors with a large field of view and detectors with a small field of view. The tests presented in this paper do not require special phantoms or sources other than those used for quality control of stationary gamma cameras. They can be applied for acceptance testing and for performance testing in a regular quality assurance programme.

Cerebral blood flow during migraine attacks without aura and effect of sumatriptan.

OBJECTIVE: To study regional cerebral blood flow (rCBF) during migraine attacks without aura and after treatment with sumatriptan. DESIGN AND INTERVENTION: We performed three technetium Tc99m hexemethyl-propyleneamineoxime single photon emission computed tomography scanning procedures in patients with migraine who participated in a double-blind, placebo-controlled, randomized clinical trial (1) outside an attack, (2) during an attack, and (3) after treatment of the attack with 6 mg of subcutaneous sumatriptan. SETTING: University hospital. PATIENTS: We studied 20 patients with migraine without aura, 15 of whom were evaluated under all three conditions and five of whom were evaluated under only two conditions. OUTCOME MEASURES: The single photon emission computed tomographic images were evaluated semiquantitatively with regard to (1) the degree of asymmetry of the rCBF between the headache side and the nonheadache side and (2) the ratio of the rCBF in regions of interest to the rCBF in two reference areas (cerebellum or frontal cortex). RESULTS: We found no significant rCBF asymmetries outside or during the attack or after treatment with sumatriptan, and there were no significant changes of the rCBF ratios during the attack (compared with outside the attack) or after treatment of the attack (compared with during the attack). CONCLUSION: Migraine attacks without aura and treatment of the attacks with 6 mg of subcutaneous sumatriptan are not associated with detectable focal changes of the rCBF.

Dual photon absorptiometry for bone mineral measurements using a gamma camera.

A gamma camera was equipped with a special collimator and arm assembly for bone mineral measurements with dual photon absorptiometry (DPA). The system was evaluated in vitro and in vivo and compared both with a rectilinear DPA and a dual energy X-ray (DEXA) system. All 3 systems showed a linear response in measurements of 4 vials, containing different amounts of hydroxyapatite. Phantom measurements with the gamma camera system showed a precision of 1.6% to 2.8%. Results obtained in 8 healthy volunteers with rectilinear and gamma camera systems were well correlated (R2 = 0.78). With the photon beam directed from posterior to anterior, the separation of vertebrae was easy with the gamma camera system. We conclude that bone mineral measurements can be made with a gamma camera for assessment of fracture risk and in the decision process whether a patient needs treatment or not. For follow-up, the precision of DPA with a gamma camera is inadequate.

Protocols for selection of cardiac radionuclide studies for use as a data base of normal studies and typical patterns of diseases. COST B2 Working Group II, in association with relevant working/task groups of the European Association of Nuclear Medicine and the European Society of Cardiology.

A data base of clinical studies is required for quality assurance of software used for analysis of radionuclide cardiac imaging procedures. Studies used must be rigorously validated in terms of both the clinical condition of the patient undergoing the procedure and the imaging protocol used. Selection protocols for the creation of a software phantom data base of normal studies and three typical patterns of cardiac disease--recent transmural myocardial infarction, isolated myocardial ischaemia and dilated cardiomyopathy--have been developed by the Cardiac Working Group of the European COST B2 project in association with the Cardiac Task Group of the European Association of Nuclear Medicine and the Working Group on Nuclear Cardiology of the European Society of Cardiology. These protocols include criteria for the interpretation of qualitative and quantitative non-radionuclide data. Compliance of the clinical data with the selection criteria will have to pass scrutiny by an international team for each study used as a software phantom. The radionuclide studies encompass stress and rest myocardial perfusion studies (planar and single photon emission tomography) using thallium-201 and technetium-99m methoxyisobutylisonitrile and rest gated blood pool studies. Methods for acquisition of data are defined for each type of study and for each individual study a portfolio of all clinical data is established. A pilot study is required to investigate the problems and logistics of distributing clinical radionuclide studies between a range of computers and institutes, and to ascertain the procedures necessary for analytical comparison of the results obtained.

The acute effects of intravenous nisoldipine on left ventricular function within 24 h after acute myocardial infarction.

Nisoldipine is a calcium antagonist with potent coronary vasodilating effects in patients with chronic stable angina pectoris. We studied the acute effects of nisoldipine in six patients within 24 h (mean 14 +/- 4 h) after the onset of myocardial infarction. Nisoldipine was administered as a 4.5 micrograms kg-1 intravenous bolus over 3 min followed by intravenous infusion of 0.2 microgram kg-1 min-1 during 60 min. Radionuclide angiography, cardiac output and intra-arterial blood pressure measurements were performed before and during nisoldipine. Left ventricular ejection fraction increased from 48.3 +/- 10.3% to 55.3 +/- 11.8% (P = 0.034) during nisoldipine infusion. Regional wall motion score changed during nisoldipine infusion from 3.3 +/- 2.5 to 1.8 +/- 2.6 (P = 0.027). Cardiac output increased from 5.5 +/- 1.0 to 7.3 +/- 1.3 l min-1 (P = 0.0001). Heart rate increased from 78 +/- 12 to 88 +/- 11 beats.min-1 (P = 0.004). Mean arterial blood pressure decreased from 91.7 +/- 20.2 to 78.7 +/- 13.1 mmHg (P = 0.038). The rate-pressure product did not change significantly during nisoldipine infusion. It is concluded that nisoldipine improves global and regional left ventricular function in patients with acute myocardial infarction within the first 24 h. Our findings suggest that this effect is achieved without increasing myocardial oxygen demand.

Assessment of acute myocardial infarction by nuclear imaging techniques.

In recent years, nuclear cardiology techniques have been successfully applied in patients with acute myocardial infarction. These scintigraphic measurements have provided important diagnostic, therapeutic, and prognostic information based on the extent of myocardial damage and the functional reserve of the left ventricle. In particular, in the thrombolytic era, myocardial perfusion imaging and radionuclide angiography have been shown to be valuable methods for studying the effects of reperfusion on the extent of myocardial damage. Nuclear magnetic resonance imaging, preferably with contrast enhancement, is one of the newly developed nuclear imaging techniques that have probably the greatest potential in accurately delineating myocardial infarct size and in evaluating left ventricular function. Radionuclide procedures, on the other hand, employ more biologically oriented tracers and are therefore capable of monitoring biochemical changes in the course of acute myocardial infarction.

Optimization of follow-up measurements of bone mass.

In bone densitometry, the precision of the instrument, the number of measurements and the time-points of the measurements are important criteria for monitoring bone mass changes. The most appropriate follow-up procedure can be determined by numerical comparison of various combinations of these three criteria. This can be done by computing the confidence interval of changes in bone mass. We developed a model to estimate the length of a confidence interval for the observed changes in individual patients. With specific instrument precision, a specified number of measurements and, assuming a linear rate of bone mass changes, the best estimate of the actual changes in bone mass is obtained by measurements at the end of an observation period. With the current precision of bone densitometers, follow-up of patients with yearly duplicate measurements is recommended. A shorter scan time interval offers no additional information unless very rapid bone loss is expected.

Magnetic resonance imaging of myocardial infarction: correlation with enzymatic, angiographic, and radionuclide findings.

Spin-echo cardiac magnetic resonance imaging studies were performed in 20 patients with a first 7- to 14-day-old (mean 10) myocardial infarction. The magnetic resonance imaging findings were compared with coronary angiography (14 patients), myocardial enzyme release (18 patients), radionuclide angiography (19 patients), and thallium-201 perfusion scintigraphy (19 patients). Regional T2 relaxation times determined from the signal intensities at echo times 30 msec and 90 msec were significantly prolonged in the infarcted areas. Based on abnormal T2 times for every patient, a regional and a total myocardial damage score was determined. The infarct-related artery was correctly identified in 93% of patients by magnetic resonance imaging, in 79% of patients by thallium-201 scintigraphy, and in 62% of patients by radionuclide angiography. The total damage score correlated well with enzymatic infarct size (r = 0.75, p less than 0.001). The correlation between left ventricular end-systolic volume index determined by magnetic resonance imaging and by radionuclide angiography was r = 0.89 (p less than 0.002). The left ventricular end-systolic volume index correlated significantly with enzymatic infarct size (r = 0.72, p less than 0.001), total damage score (r = 0.68, p less than 0.002), and radionuclide left ventricular ejection fraction (r = -0.68, p less than 0.002). Correlations between the magnetic resonance damage score and the thallium-201 perfusion score were r = 0.60 (p less than 0.01) for the exercise images, and r = 0.72 (p less than 0.001) for the redistribution images. This study shows that spin-echo magnetic resonance imaging is quite comparable with the established noninvasive imaging modalities currently used in patients with acute myocardial infarction.

The diagnostic value of immediate post-exercise left ventricular ejection fraction (LVEF).

The diagnostic value of immediate post-exercise left ventricular ejection fraction (LVEF) was assessed in 161 patients at rest, during maximal exercise, and immediately post-exercise by radionuclide angiography. Fifteen patients had a second examination, giving a total of 176 radionuclide examinations. Additionally, the correlation between post-exercise LVEF and physical validity was investigated. Sixty-one patients (35%) with a recent myocardial infarction (less than 4 weeks), 66 patients (37%) with an old myocardial infarction (greater than 4 weeks), and 21 patients (12%) with valvular lesions were studied. Twenty-eight patients (16%) with an abdominal aneurysm were considered as controls based on history and a normal resting and exercise electrocardiogram (ECG). LVEF and a cumulative regional wall motion (RWM) score for three regions were obtained. LVEF post-exercise was significantly increased compared to LVEF at maximal exercise in all four diagnostic groups. Absolute LVEF values were significantly dependent on the level of exercise. We conclude that immediate post-exercise LVEF should not be used for separating patients with and without coronary artery disease.

Automated comparison of dual-photon absorptiometric studies of the lumbar spine.

An automated image comparison procedure was developed to optimize the precision of bone mineral density measurements by dual-photon absorptiometry. Changed acquisition conditions cause differences between two images to be compared. Alignment of one image with respect to the other is performed by a transformation that involves a rotation, a horizontal or vertical shift, and a correction for the soft tissue level. The best possible transformation is found in a stepwise search, guided by initial estimations of its parameters. After optimum transformation of one image, the region of interest of the other image is applied to both of them. Duplicate measurements of 9 patients and 15 normal subjects were performed; automated analysis yielded improved precision with respect to manual analysis. The coefficient of variation (CV) was also computed. The CV for automated analysis was 2.00% for patients and 1.04% for normal subjects compared to 3.55 and 1.93%, respectively, for manual analysis. For phantoms, the precision was 2.67% for manual analysis and 0.49% for automated analysis.

Influence of angiotensin converting enzyme inhibition on pump function and cardiac contractility in patients with chronic congestive heart failure.

Eleven patients with coronary artery disease and chronic heart failure were studied before and three months after the angiotensin converting enzyme inhibitor enalapril was added to their frusemide medication. The following were measured: left ventricular pressure and volume with transient occlusion of the inferior vena cava, radionuclide angiography, and hormone concentrations in plasma. As in other reported studies, the clinical condition of the patients improved and their exercise tolerance increased moderately. Addition of enalapril reduced end diastolic and systolic pressure, reduced ventricular volume, and concomitantly increased the ejection fraction. The end systolic pressure-volume relation shifted to the left as it did in a similar animal study. In the animal study unloading by a vasodilator did not induce a leftward shift, so it can be inferred that in the present study unloading combined with a decrease in the angiotensin concentration was instrumental in remodelling the heart. Though unloading was expected to have a beneficial effect on the oxygen supply/demand ratio of the heart, the patients still showed the same drop in the ejection fraction during exercise as they did before treatment with enalapril, and early diastolic filling did not improve. Normally, regression of cardiac dilatation is only found if pump function improves; the present study showed that unloading in combination with angiotensin converting enzyme inhibition reshapes the ventricle without improving intrinsic pump function.

Improvement of left ventricular function in silent ischemia following myocardial infarction, after administration of diltiazem.

In a group of 72 patients with acute myocardial infarction who underwent a maximal symptom-limited predischarge exercise test in conjunction with radionuclide angiography, 25 (35%) showed greater than 1 mm asymptomatic ST-T-segment depression during exercise. All 25 patients underwent repeated exercise radionuclide angiography 2 days later, 2 h after oral intake of 120 mg diltiazem. Double product was not significantly different before and after diltiazem both at rest and during exercise. Maximal ST-T-segment depression after diltiazem was reduced from 2.4 +/- 0.9 mm to 0.8 +/- 0.6 mm (p less than 0.01). Left ventricular ejection fraction (LVEF) at rest was (before diltiazem) 52.1 +/- 8.9% and (after diltiazem) 55.1 +/- 12.3% (NS). During exercise, LVEF improved after diltiazem from 42.8 +/- 12.1% to 49.1 +/- 10.8% (p less than 0.05). Regional wall motion score (1 = normal, 2 = hypokinetic, 3 = akinetic, 4 = dyskinetic) at rest before diltiazem was 9.9 +/- 2.3 and, after diltiazem, was 9.0 +/- 1.9 (NS). During exercise, regional wall motion score improved after diltiazem from 5.9 +/- 1.3 to 4.2 +/- 1.2 (p less than 0.02). We conclude that diltiazem has acute beneficial effects on asymptomatic ST-T-segment depression and on global and regional left ventricular function in post-infarction patients with silent ischemia.

Limited precision of lumbar spine dual-photon absorptiometry by variations in the soft-tissue background.

The estimation error due to variations in soft-tissue baseline in lumbar bone mineral content (BMC) measured by dual-photon absorptiometry (DPA) was calculated with a new method of automatic baseline subtraction. In water phantom measurements, the s.d. of the soft-tissue (ST) baseline matched closely (r = 0.98) to the random error, calculated using 44 keV and 100 keV count rates and the directly determined baseline variations. In 21 volunteers and in 70 patients with osteoporosis, the ST variations were larger than the expected random error, revealing a source of error related to the inhomogeneity of soft tissue. The estimation error in BMC caused by ST variations was 0.7% in healthy subjects (mean BMC 40.5 gHA) and 1.5% in patients (mean BMC = 26.4 gHA). These results indicate that ST-related errors are an important limit to the precision of lumbar DPA measurements.

Comparison of four commercially available 81Rb-81mKr generators: quality testing using a breathing lung phantom.

Four commercially available 81Rb-81mKr generators, including their elution systems, were compared. Considerable differences in useful output between the various generators were found. When a standardized elution system was used, the differences became much less. Differences in the tubing and inaccuracy of the flow meters were found to be the major causes of the original differences. The user should be aware of a loss of output that may occur when the generator is eluted with dry air.

Short-term and long-term changes of left ventricular volumes during rate-adaptive and single-rate pacing.

To evaluate the adaptation of the heart to exercise during pacing, 15 patients with permanent endocardial pacemakers were studied; nine patients had atrioventricular universal (DDD) pacemakers (Symbios 7005) and six patients had activity detecting rate-responsive ventricular (VVIR) pacemakers (Activitrax 8403). Left ventricular function in each patient during rate variable pacing was compared to ventricular function during VVI single-rate pacing. End-systolic and end-diastolic volume changes during exercise were measured by radionuclide angiography and the amount of volume change was used to assess left ventricular function. Both short-term (within 4 hours) and long-term measurements (after at least 4 weeks) were made at rest and at 50% of the maximal exercise capacity in DDD or VVIR mode and were compared with VVI single-rate pacing. All patients, when changed from DDD or VVIR mode to VVI single-rate pacing showed a significant increase of the end-diastolic volume during exercise, which increased even more after long-term VVI pacing. During long-term rate variable pacing, there was no increase of the end-diastolic volume during exercise. DDD or VVIR pacing initially showed a substantial increase of the end-systolic volume during exercise combined with a decrease of left ventricular ejection fraction, suggesting a decrease of the left ventricular contractility. After 4 weeks, contractility improved both with DDD and VVIR pacing. We conclude that short-term DDD and VVIR pacing induces a temporary impairment of left ventricular function that improves after 4 weeks, whereas long-term VVI pacing is associated with left ventricular dilatation even at moderate levels of exercise.