Proportional anatomical stereotactic atlas for visual interpretation of brain SPET perfusion images

A semi-automatic method was developed to determine the anterior (AC) and posterior (PC) commissures on brain single-photon emission tomographic (SPET) perfusion images, and then to draw the proportional anatomical Talairach's grid on each axial SPET image. First, the AC-PC line was defined on SPET images from the linear regression of four internal landmarks (frontal pole of the brain, inferior limit of the anterior corpus callosum, sub-thalamic point and occipital pole). Second, the SPET position of AC and PC points on the AC-PC line was automatically determined from measurements made on hard copies of magnetic resonance (MR) images of the patients. Finally, a proportional Talairach's grid was automatically drawn on each axial SPET image. To assess the accuracy of localization of AC and PC points, co-registered technetium-99m hexamethylpropylene amine oxime SPET and MR images from 11 subjects were used. The mean displacements between estimated points on SPET and true points on MRI (x=sagittal, y=frontal and z=axial displacement) were calculated. The mean displacements (in mm) were x=–1.4±1.8, y=–1.7±3.3 and z=–1.1±2.5 for AC, and x=–1.8±1.8, y=0.3±3.2 and =–1.3±2.7 for PC. These displacements represented an error of less than 5 mm at the anterior or posterior pole of the brain or at the vertex. Intra- and inter-observer comparisons did not reveal significant differences in mean displacements. Thus, this semi-automatic method results in reproducible and accurate stereotactic localization of SPET perfusion abnormalities. This method can be used routinely for repeat follow-up studies in the same subject as well as in different individuals without requiring SPET MRI co-registration.     

Influence of intravenously administered lidocaine on cerebral blood flow in a baboon model standardized under controlled general anaesthesia using single-photon emission tomography and technetium-99m hexamethylpropylene amine oxime

The baboon under general anaesthesia as a model to assess drug-induced cerebral blood flow changes ( CBF) using single-photon emission tomography (SPET) offers great in vivo possibilities but has to comply with demands on control of anaesthesia-related influencing factors, such as P _aCO₂ changes. The model sought in this study and described here allows control of P _aCO₂, in the baboon under thiopentone anaesthesia by ventilation, and was evaluated for the functional dependence of CBF vs P _aCO₂, using SPET technetium-99m hexamethylpropylene amine oxime (HMPAO) and the split-dose method together with controlled ventilation. During the experiment the model was validated for normal reactivity to P _aCO₂ changes, and subsequently applied to investigate the mechanisms (still uncertain) of CBF increase known to follow administration of the local anaesthetic lidocaine. Six baboons received 6 mg/kg lidocaine intravenously. CBF was measured between two consecutive SPET acquisitions (split-dose method) respectively relating to HM-PAO distributions in the brain before and after the injection of lidocaine. Meanwhile the animals were maintained at constant respiratory rate and volume. The results indicate that the correlation between CBF and the ensuing fall in P_aCO₂ deviated from the baseline pattern from the model and confirmed a cerebrovascular contribution to the lidocaine-induced CBF increase. This agreed well with mean and systolic blood pressure changes and heart rate. Correspondence to: I.C. Dormehl     

Stress induced right ventricular dysfunction: An indication of reversible right ventricular ischaemia

Stress induced changes in left ventricular ejection fraction are widely used in the detection and assessment of coronary artery disease. This study demonstrates that right ventricular dysfunction may also occur, and assesses its significance in terms of coronary artery anatomy. This study involved 14 normal subjects and 26 with coronary artery disease investigated by equilibrium radionuclide ventriculography, at rest and during maximal dynamic exercise. Mean normal resting right ventricular ejection fraction (RVEF) was 0.40 (SD 0.118), and all normal subjects increased RVEF with stress (mean RVEF+0.13 SD 0.099). Mean RVEF in the subjects with coronary artery disease was significantly lower at 0.00 (SD 0.080), but there was overlap between the two groups. The largest falls in RVEF were seen if the right coronary artery was occluded without retrograde filling. In this subgroup with the most severely compromised right ventricular perfusion (nine subjects), RVEF always fell with stress, and mean RVEF was-0.08 (SD 0.050). There was no significant correlation between LVEF and RVEF, implying that the right ventricular dysfunction was due to right ventricular ischaemia, rather than secondary to left ventricular dysfunction. Stress induced right ventricular ischaemia can therefore be detected readily by radionuclide ventriculography.     

Quantification of left ventricular size on exercise thallium-201 single-photon emission tomography

The purposes of this study were to determine whether quantification of the left ventricular size on exercise thallium-201 single-photon emission tomography (SPET) correlates with echocardiographic measurements, whether the quantification reflects the severity of coronary artery disease, and whether it can provide supplementary information regarding the severity of coronary artery disease. In 42 control subjects and 110 patients who underwent coronary angiography, we performed exercise²⁰¹Tl SPET and quantified six non-regional markers: lung²⁰¹Tl uptake on an initial planar image (Lung/Heart), left ventricular width on a tomogram (Width), change in the Width from the initial to delayed tomograms (Width), count ratio of the left ventricular cavity to the myocardium (C/M), count ratio of the lung to the myocardium (UM), and count ratio of the lung to the left ventricular cavity (L/C). In 76 patients, furthermore, the Width was compared with echocardiographic measurements. The Width correlated with echocardiographic measurements (P<0.001). The Width and Width were significantly different among zero-, one-, two- and three-vessel disease (P<0.001). However, the Width and Width could not improve the power of discrimination for multi-vessel disease derived from the Lung/Heart. The six non-regional markers correlated with each other (P<0.001). Among the six markers, the Lung/Heart was only the independent discriminator for multi-vessel disease. In conclusion, quantification of the left ventricular size on exercise²⁰¹Tl SPET correlated with echocardiographic measurements and reflected the severity of coronary artery disease, but may be replaced with quantitation of the lung²⁰¹Tl uptake.     

Stability of α-[11C]methyl-l-tryptophan brain trapping in healthy male volunteers

Purpose The purpose of this study was to assess the reproducibility in healthy volunteers of -[¹¹C]methyl-l-tryptophan ([¹¹C]MT) brain trapping imaging with positron emission tomography (PET), using volumes of interest (VOIs) and voxel-based image analysis.Methods Six right-handed healthy male volunteers (34.3±10.9 years) with a negative family history for psychiatric disorders were scanned twice in the resting condition, 22±17 days apart. An unbiased semiautomatic segmentation of the brain was used to define VOIs. The trapping constant K* (ml g^–1 min^–1) for [¹¹C]MT was calculated for the whole brain and seven brain regions using the graphical method for irreversible tracers. In addition, parametric maps of K* were obtained from dynamic scans using the same method. Comparison of test and retest K* functional images was performed using SPM99. Students paired t statistic was applied for comparisons of [¹¹C]MT brain trapping in a priori selected VOIs.Results [¹¹C]MT brain trapping in VOIs showed a mean variability 2.6±1.8% (0.3–5%) for absolute and 1.5±2.1% (1.4–4.1%) for normalized K*. Intraclass correlations between test and retest conditions were 0.61±0.34 for absolute K* values and 0.73±0.20 for K* values normalized by global mean. SPM99 analysis using a height threshold of p=0.05 (two tailed) and an extent threshold of 100 voxels showed no significant differences between scans.Conclusion Rest measurements in healthy male volunteers of the trapping constant for [¹¹C]MT, using PET, appeared to be stable during an average interval of 3 weeks.     

Use of 11C-triphenylmethylphosphonium for the evaluation of membrane potential in the heart by positron-emission tomography

The membrane potential in cells can be estimated by electrophysiological techniques and biomedical methods using lipophilic cations labelled with ¹⁴C. However, these techniques cannot be applied to the human heart. In this study a lipophilic cation, triphenylmethylphosphonium (TPMP), was labelled with carbon-11 with the purpose of investigating its suitability for the estimation of membrane potential in vivo. A biodistribution study in mice and rats showed significant uptake of the cation in the heart a few minutes after IV injection which remained constant for 60 min. In vivo study by positron-emission tomography showed that after IV injection of ¹¹C-TPMP in the dog, activity rose almost immediately in the myocardium and then remained constant for 60 min. A rapid injection of KCl (>40 mg/kg) 20 min after injection of ¹¹C-TPMP led to an instantaneous fall in myocardial ¹¹C-TPMP concentration. Membrane potential (), calculated from the TPMP distribution ratio between intracellular and plasma water space by the Nernst equation, was estimated at-148.1±6.0 mV for the dog heart. This value reflected both cell membrane potential and mitochondrial membrane potential and thus, the energy state of the myocardial cells.     

Can pre-operative contrast-enhanced dynamic MR imaging for prostate cancer predict microvessel density in prostatectomy specimens?

The aim of this study was to correlate quantitative dynamic contrast-enhanced MRI (DCE MRI) parameters with microvessel density (MVD) in prostate carcinoma. Twenty-eight patients with biopsy-proven prostate carcinoma were examined by endorectal MRI including multiplanar T2- and T1-weighted spin-echo and dynamic T1-weighted turbo-FLASH MRI during and after intravenous Gd-DTPA administration. Microvessels were stained on surgical specimens using a CD31 monoclonal antibody. The MVD was quantified in hot spots by counting (MVC) and determining the area fraction by morphometry (MVAF). The DCE MRI data were analyzed using an open pharmacokinetic two-compartment model. In corresponding anatomic locations the time shift (t) between the beginning of signal enhancement of cancer and adjacent normal prostatic tissue, the degree of contrast enhancement and the contrast exchange rate constant (k₂₁) were calculated. The MVC and MVAF were elevated in carcinoma (p<0.001 and p=0.002, respectively) and correlated to k₂₁ (r=0.62, p<0.001 and r=0.80, p<0.001, respectively). k₂₁-values of carcinoma were significantly higher compared with normal peripheral but not central zone tissue. t was longer in high compared with low-grade tumors (p=0.025). The DCE MRI can provide important information about individual MVD in prostate cancer, which may be helpful for guiding biopsy and assessing individual prognosis.     

A pragmatic approach to metal artifact reduction in CT: merging of metal artifact reduced images

The purpose of this study was to improve metal artifact reduction (MAR) in X-ray computed tomography (CT) by the combination of two artifact reduction methods. The presented method constitutes an image-based weighted superposition of images processed with two known methods for MAR: linear interpolation of reprojected metal traces (LI) and multi-dimensional adaptive filtering of the raw data (MAF). Two weighting concepts were realized that take into account mean distances of image points from metal objects or additional directional components. Artifact reduction on patient data from the jaw and the hip region shows that although the application of only one of the MAR algorithms can already improve image quality, these methods have specific drawbacks. While MAF does not correct corrupted CT values, LI often introduces secondary artifacts. The corrective impact of the merging algorithm is almost always superior to the application of only one of the methods. The results obtained with directional weighting are equal to or in many cases better than those of the distance weighting scheme. Merging combines the advantages of two fundamentally different approaches to artifact reduction and can improve the quality of images that are affected by metal artifacts.Symbols LI linear interpolation algorithm - MAF multi-dimensional adaptive filtering algorithm - MAR metal artifact reduction - f(x, y) object function at (x, y) - F(), F() normalized filter function in the direction of the coordinates and - I primary X-ray intensity - I₀ transmitted X-ray intensity - N_D number of detectors per detector row - p attenuation - p(,), p(,) projection data (fan and parallel geometry) - p_th lower threshold of the attenuation of adaptive filtering - p_max maximum value of the attenuation of adaptive filtering - (x, y) image point - projection angle in fan geometry - angle within the fan relative to the central ray - , , z, , minimum functions for adaptive filtering - projection angle in parallel geometry - orthogonal distance of a ray to the center of rotation in parallel geometry     

Effects of partial volume correction on discrimination between very early Alzheimer’s dementia and controls using brain perfusion SPECT

We assessed the accuracy of brain perfusion single-photon emission computed tomography (SPECT) in discriminating between patients with probable Alzheimers disease (AD) at the very early stage and age-matched controls before and after partial volume correction (PVC). Three-dimensional MRI was used for PVC. We randomly divided the subjects into two groups. The first group, comprising 30 patients and 30 healthy volunteers, was used to identify the brain area with the most significant decrease in regional cerebral blood flow (rCBF) in patients compared with normal controls based on the voxel-based analysis of a group comparison. The second group, comprising 31 patients and 31 healthy volunteers, was used to study the improvement in diagnostic accuracy provided by PVC. A Z score map for a SPECT image of a subject was obtained by comparison with mean and standard deviation SPECT images of the healthy volunteers for each voxel after anatomical standardization and voxel normalization to global mean or cerebellar values using the following equation: Z score = ([control mean]–[individual value] )/(control SD). Analysis of receiver operating characteristics curves for a Z score discriminating AD and controls in the posterior cingulate gyrus, where a significant decrease in rCBF was identified in the first group, showed that the PVC significantly enhanced the accuracy of the SPECT diagnosis of very early AD from 73.9% to 83.7% with global mean normalization. The PVC mildly enhanced the accuracy from 73.1% to 76.3% with cerebellar normalization. This result suggests that early diagnosis of AD requires PVC in a SPECT study.     

Quantification of left ventricular volume in gated equilibrium radioventriculography

We have developed a simple method for measuring left ventricular volume based on semi-automated analysis of 40° left anterior oblique images obtained with a standard scintillation camera after equilibrium of an intravenous injection of 20 mCi of technetium-99m in vivo labeled red blood cells. The essence of the method is the use of the dimensions and radioactivity within a segment of aorta to convert observed left ventricular count rates to volume. Four assumptions were made: 1) the aortic arch is nearly parallel to the collimator face when a patient is in the proper left anterior oblique position; 2) a segment at the top of the aortic arch, approximately 1 cm wide, is a right cylinder, 3) the edges of the aorta can be delineated as the lines where the second derivative of a cross sectional profile equals zero; 4) left ventricular and aortic arch counts undergo the same attenuation because they are nearly the same distance from the chest wall in the proper left anterior oblique position. By measuring the counts and volumes of two regions of known shape, one in the middle, the other at the edge of the aortic arch, and calculating their differences a background-independent volume count ratio (v/C) can be obtained. The left ventricular and diastolic volume (LVEDV) is calculated with the equation: LVEDV=(/C) LVEDC, where LVEDC represents left ventricular end diastolic counts. Twenty-six patients were evaluated by equilibrium radio- and contrast-ventriculography, the latter analyzed by planimetry. The radionuclide method yielded an end diastolic volume that correlated well with contrast ventriculography (r=0.96, Y=0.91 X+21 ml). In addition to its simplicity and objectivity, a major advantage of this method of determining ventricular volume is that it does not require a blood sample.This work was supported in part by USPHS Grant Nos. HL 20674 and GM 10548     

Technical parameters influencing the severity of injury of front-seat,belt-protected car passengers on the impact side in car-to-car side collisions with the main impact between the front and rear seats (B-pillars)

Summary Authentic car-to-car side collisions (n = 30) with the main impact area at the B-pillar were analyzed to find technical parameters corresponding with the injury severities of the front seat, belt-protected car passengers on the impact side. EES (Energy Equivalent Speed) and Av (delta v, change in velocity) were highly significant predictors of the severity of thoracic and abdominal injuries and total injury severity coded according to the Abbreviated Injury Scale (AIS). At an EES or v 40 km/h all front-seat car passengers on the impact side sustained a total injury severity of Maximum AIS (MAIS) 4 and died. Although a passenger could survive the crash without injury to one or more body regions up to the highest EES- and Av-values, at EES or v 40 km/h fatal injuries were sustained in at least one body region. At an EES 35 km/h or a Av 15 km/h no front-seat car passenger on the impact side remained uninjured.     

A quantitative assessment of scintigraphy of the legs using 201Tl

²⁰¹Tl perfusion scintigraphy of the legs was evaluated to define intermittent claudication quantitatively, based on Sapirstein's indicator fractionation principle. After intravenous injection of ²⁰¹Tl with or without exercise, the distribution of the radiotracer throughout the body was obtained using the whole body scanner. Regional blood flow of cardiac output for three segments of the leg was estimated as a regional fractional uptake (rFU) distributed in these segments compared with the whole body distribution. The validity of the principle was confirmed by a comparative study with ^99mTc-MAA (r=0.979). Normal rFUs (%) for each section at rest and after stress, respectively, were 5.49±0.69 and 19.40±2.04 (whole leg); 3.57±0.49 and 12.26±1.91 (thigh); 1.59±0.34 and 6.58±0.61 (calf). The rates of rFU change from the state of rest to stress (rFU) in normals were 3.41±0.45 (whole leg), 3.44±0.61 (thigh), and 4.30±1.03 (calf). Although rFU was within normal limits in patients with arteriosclerosis obliterans (ASO) and thromboangitis obliterans (TAO), rFU of the whole leg was significantly decreased from the normal value of 3.41±0.45 to 1.95±0.40 for ASO (P(0.001) and 1.82±0.47 for TAO (P(0.001). A defect or decreased activity on the stress scintigraph was well correlated with the angiographic findings.     

Morbus Alzheimer - Die Geschichte einer Erkrankung und die Rolle der modernen diagnostischen Radiologie

The effect of the Prandtl number (Pr) and the Reynolds number (Re) on the behaviour of weak laminar axisymmetric and plane fountains has been studied using dimensional and scaling analyses and direct numerical simulation. For Fr 1.0 and assuming viscous effects are important, the analysis shows that for both the axisymmetric and plane fountains, y_mFrRe^–1/2, where Fr is the Froude number defined at the fountain source and y_m is the non-dimensionalized fountain height. These scalings are also valid for the non-dimensionalized fountain width. The analyses also shows _msFr², where _ms is the non-dimensionalized time scale for the fountain flow in the fountain core to reach steady state, and using this time scale y_TFr(RePr)^–1/2, where y_T is the non-dimensionalized thickness of the temperature layer on the symmetry axis over which the fountain fluid temperature changes from the inlet value to that of the ambient fluid. All these scalings have been quantified by the direct numerical simulations, hence confirming in certain ranges the phenomenological scaling obtained in this paper.     

Development of a psilocin immunoassay for serum and blood samples

After the immunisation of rabbits with a psilocin-specific immunogen, polyclonal antisera were obtained. With these antisera a competitive, heterogeneous radioimmunoassay for the detection of psilocin was developed. As tracer a derivative of psilocin was synthesised, which contained a tritiated CH₃ group. The antisera showed a specific reaction with psilocin. The cross-reactivity of structurally related endogenous substances like serotonin, tryptophan and tyrosine was below 0.01%. Also common drugs of abuse (⁹-tetrahydrocannabinol, cocaine, morphine, amphetamine) showed negligible cross-reactivity (0.01–2%). Only tricyclic neuroleptics with a (dimethylamino)ethyl side-chain showed some cross-reactivity (20%). Spiked serum and blood samples were analysed with this new immunoassay and the results obtained were compared with the values measured with a validated GC-MS method.     

Quantification of technetium-99m hexamethylpropylene amine oxime brain uptake in routine clinical practice using calibrated point sources as an external standard: phantom and human studies

Quantitative methods for calculation of regional cerebral blood flow with technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) have been proposed. These methods are very labour intensive and therefore are not useful in routine clinical practice. We describe a simple alternative method, using calibrated point sources as a scaling factor, whereby the tomographic slices are displayed as regional ^99mTc-HMPAO brain uptake per cm³ brain tissue in 10^–6 of the injected lipophilic dose. The method was validated on Jaszczak and Hoffman phantoms using a three-detector system with HR parallel and HR fan-beam collimators. Under the optimal conditions described in this paper, the measured to real activity ratio was 1.00 (SD = 0.06). The reproducibility of the cerebellar uptake in a group of ten normal volunteers and five patients was studied. Intra-individually a mean deviation of 12.6% was observed for the total group. For those persons with a heart rate difference of less than 5 units between the two studies, a mean deviation of 7.2% was obtained. Quantitative ^99mTc-HMPAO brain uptake images can be useful for longitudinal studies, especially for follow-up, activation and pharmacological studies. Correspondence to: A. Dobbeleir     

Gated cardiac blood pool studies in atrial fibrillation: role of cycle length windowing

Cycle length windowing is gaining increasing acceptance in gated blood pool imaging of patients with atrial fibrillation (AF). The goals of this study were: to assess differences of ejection fraction (EF) in AF with and without windowing and to determine how EF varied with cycle length in patients with AF. Twenty patients with AF were prospectively studied by gated blood pool imaging, with simultaneous collection in each patient of 5–7 studies with cycle length windows spanning the cycle length histogram. Each window accepted beats of only a narrow range of cycle lengths. EF was determined for each of the narrow cycle length windows as well as for the entire gated blood pool study without cycle length windowing. For every patient an average of the windowed EFs was compared with the non-windowed EF. EF values were similar (mean windowed: 46.6; non-windowed: 45.5; P=0.16), and there was a good correlation between the two techniques (r=0.97). The data were then examined for a relationship of EF with cycle length. The difference from average windowed EF (EF) was calculated for each window and plotted vs. the cycle length of the center of each window. No predictable linear or nonlinear relationship of EF with window position was observed. Lack of predictable variation of EF with cycle length is likely due to lack of a predictable amount of ventricular filling for a given cycle length, as the amount of diastolic filling in AF depends on the random cycle length of the preceding beat. In summary, windowing in AF does not provide a clinically significant difference in EF determination. If cycle length windowing is used, the exact location of the window is not critical.     

Difference of 14C turnovers in brain and in transplanted glioma after intravenous injection of 14C-1-pyruvate into rats

Carbon 14 from ¹⁴C-1-pyruvate injected intravenously into glioma-transplanted rats was incorporated into various compounds in the brain and in the tumor. In the brain the majority of activity was found in CO₂ (60%), and minor activities were found in alanine, lactate (15%), glutamate, and aspartate, with decreasing order, 5 min after injection. In the tumor, at 5 min, the largest activity was in lactate (56%), and lower activities were found in CO₂ (24%), alanine, glutamate, and aspartate. The total ¹⁴C concentration in the tumor was twice that in the brain at 5 min and 15 min. The result was in accordance with the prediction that in brain, where the mitochondrial function is active, ¹⁴C-1-pyruvate will be oxidized completely into ¹⁴CO₂, and that in tumor, where the mitochondrial function is insufficient, ¹⁴C-1-pyruvate will be converted only into ¹⁴C-lactate and prevent further degradation. It may be assumed that this difference in the turnover of ¹⁴C of ¹⁴C-1-pyruvate between brain and tumor could constitute a basis for the hot visualization of human brain tumor using cyclotron-produced ¹¹C-1-pyruvate and positronemission tomography.     

Magnetization transfer ratio in neuro-Behçet disease

The aim of this study was to determine the contribution of magnetization transfer ratios (MTRs) in detecting disease in normal-appearing brain regions of patients with neuro-Behçet (NB) disease. Thirty-two patients with NB disease were assessed. Fifteen healthy volunteers were examined as the control group. Magnetic resonance (MR) imaging of the head was performed without and with magnetization transfer (MT) contrast. Signal intensity measurements were obtained from ten anatomical regions (centrum semiovale, corona radiata, internal capsule, forceps major, forceps minor, thalamus, substantia nigra pars compacta, substantia nigra pars grisea, inferior pons and middle cerebellar peduncle) in both groups. Also measured in the NB group were parenchymal lesions in the brain stem, basal ganglia and cerebral deep white matter. MTR was calculated for each measurement. Statistical analysis was performed with Mann–Whitney U and independent t-tests with computer-based SPSS 11.0 for Windows software. A P value below 0.05 was considered statistically significant. The mean MTR of the parenchymal lesions in the NB group was lower than the mean MTR of the normal-appearing parenchyma in both the NB patients and the normal group. For the normal-appearing parenchyma the mean MTR in the NB group was higher than that for the controls for all regions except the corona radiata; however, the difference was statistically significant only for the thalamus. The MRI-visible parenchymal involvement of Behçets disease causes a decrease in MTR. For the normal-appearing brain, although lacking statistical significance for the most regions studied, the tendency for higher MTR in NB patients compared with controls may offer an insight into the pathophysiology of Behçets disease.     

Non-invasive assessment of distribution volume ratios and binding potential: tissue heterogeneity and interindividually averaged time-activity curves

Due to the stochastic nature of radioactive decay, any measurement of radioactivity concentration requires spatial averaging. In pharmacokinetic analysis of time-activity curves (TAC), such averaging over heterogeneous tissues may introduce a systematic error (heterogeneity error) but may also improve the accuracy and precision of parameter estimation. In addition to spatial averaging (inevitable due to limited scanner resolution and intended in ROI analysis), interindividual averaging may theoretically be beneficial, too. The aim of this study was to investigate the effect of such averaging on the binding potential (BP) calculated with Logans non-invasive graphical analysis and the simplified reference tissue method (SRTM) proposed by Lammertsma and Hume, on the basis of simulated and measured positron emission tomography data {[¹¹C]d-threo-methylphenidate (dMP) and [¹¹C]raclopride (RAC) PET}. dMP was not quantified with SRTM since the low k ₂ (washout rate constant from the first tissue compartment) introduced a high noise sensitivity. Even for considerably different shapes of TAC (dMP PET in parkinsonian patients and healthy controls, [¹¹C]raclopride in patients with and without haloperidol medication) and a high variance in the rate constants (e.g. simulated standard deviation of K ₁=25%), the BP obtained from average TAC was close to the mean BP (error <5%). However, unfavourably distributed parameters, especially a correlated large variance in two or more parameters, may lead to larger errors. In Monte Carlo simulations, interindividual averaging before quantification reduced the variance from the SRTM (beyond a critical signal to noise ratio) and the bias in Logans method. Interindividual averaging may further increase accuracy when there is an error term in the reference tissue assumption E=DV ₂–DV (DV ₂ = distribution volume of the first tissue compartment, DV = distribution volume of the reference tissue). This can be explained by the fact that the distribution volume ratio (DVR=DV/DV) obtained from averaged TAC is an approximation for DV/DV rather than for DVR/n. We conclude that Logans non-invasive method and SRTM are suitable for heterogeneous tissues and that discussion of group differences in PET studies generally should include qualitative and quantitative assessment of interindividually averaged TAC.     

Iodine-125 labeled phenylphosphonic acid: A new radiopharmaceutical for long-term investigations of the skeleton

A skeletal seeking radiopharmaceutical labeled with a long-lived radionuclide was developed to evaluate regional bone formation and its subsequent resorption. The agent is [phosphonate (phenylmethylene hydroxy) bis]-I-125 or I-125 PA. Tissue distribution studies in mice (N=16) showed approximately 40% of the administered dose to be retained by the skeleton up to 336 hours post IV injection. The percentage of the dose accumulated by the thyroid gland remained at less than 0.5%, indicating minimal deiodination of the I-125 PA. Whole body retention studies in the same species revealed a triexponential release pattern with the longest component comprising 33% of the dose with a biologic half-life of 962 days. A fractured rat tibia model was studied with I-125 PA and Tc-99^m MDP. Chronic loss of the I-125 PA relative to normal tibia was quantitated: five days (62.8%); 30 days (47.4%). Concomitant increased uptake of the Tc-99^m MDP was observed at the fracture site relative to normal: five days (186%); 30 days (1,041%). The above data suggest that I-125 PA can be utilized to measure acute bone formation and chronic resorption.