Wolfram H. Knapp

Attenuation correction by simultaneous emission-transmission myocardial single-photon emission tomography using a technetium-99m-labelled radiotracer : impact on diagnostic accuracy

Irregular photon attenuation may limit the diagnostic accuracy of myocardial single-photon emission tomography (SPET). The aim of this study was to quantify the potential benefit of attenuation correction by simultaneous emission and transmission imaging for the detection of coronary artery disease (CAD) of vessels supplying the inferoposterior wall segments. In 25 male patients with ≥50% stenoses of the right coronary artery and/or circumflex artery but without significant narrowing of the left anterior descending artery, stress studies using technetium-99m tetrofosmin (400 MBq) were carried out with and without attenuation correction. A dual-head camera with L-shaped detector positioning was equipped with two scanning gadolinium-153 line sources. Tomograms were reconstructed and quantified using circumferential count rate profiles of myocardial activity (two in each patient). The profiles were compared with the respective normal ranges obtained from a database of 25 male patients with a <10% likelihood of CAD. In patients without CAD, the maximal differences in count density of different wall segments were reduced from 29.0% in non-corrected (NC) studies to 9.5% in attenuation-corrected (AC) studies. In particular, the inferoposterior and septal wall segments were represented by significantly increased relative count densities after attenuation correction. The effects of attenuation correction proved independent of body mass. In patients with CAD, segmental count densities were abnormal in 84% of the NC studies and 100% of the AC studies. In single-vessel disease the stenotic vessel was identified in 66% of cases by NC studies and in 100% by AC studies. In AC studies, the extent and depth of defects exceeded those in NC studies. For the detection of CAD of the right coronary artery, the receiver operating characteristic (ROC) curves relating to the AC studies demonstrated improved discrimination capacity (P<0.05). ROC analysis of CAD detection yielded normalcy rates of 82% (NC) and 94% (AC) for the circumflex artery and 65% (NC) and 97% (AC) for the right coronary artery area at a sensitivity level of 95%. It is concluded that attenuation correction using the above system may enhance the diagnostic accuracy of myocardial SPET when inferoposterior wall segments are to be evaluated.

Positive correlation between reduction of handwriting area and D2 dopamine receptor occupancy during treatment with neuroleptic drugs

We investigated the relationship between fine extrapyramidal-motor symptoms (reduction of handwriting area) and D2 dopamine receptor occupancy under neuroleptic treatment. The handwriting of 18 schizophrenic patients before and during treatment with typical (haloperidol, haloperidol decanoate) and atypical (clozapine, risperidone) neuroleptic drugs was examined. Data analysis of the handwritings examination was carried out with a planimetric computer programme. At the time of the second test of handwriting, D2 receptor occupancy was determined with single photon emission tomography (SPET) using [(123)I]iodobenzamide ((123)I-IBZM). In all patients, a reduction of handwriting area and a D2 receptor occupancy were found. The correlation between reduction of handwriting area and D2 receptor occupancy for typical and atypical neuroleptic drugs was linear and statistically significant (r=0.9; P > 0.001). Our findings point to the possibility that the reduction of handwriting area may be used as a clinical indicator of D2 receptor occupancy under treatment with neuroleptic drugs.

Age-specific cerebral perfusion in 4- to 15-year-old children: a high-resolution brain SPET study using 99mTc-ECD.

Abstract.This study addresses the question of whether the normal range for distribution of local cerebral blood flow (lCBF) in adults can be transferred to the 4- to 15-year-old age group. Twenty-three children (age: 4–15 years; mean 11±3 years, group I) and 10 adults (age: 27–56 years; mean 45±10 years, group II) without evidence of cerebrovascular disease or other brain diseases underwent technetium-99m ethyl cysteinate dimer single-photon emission tomography. Counts in cortical and subcortical regions of interest (ROIs) were related to those in cerebellar ROIs (= 100%). Relative cortical activity in group I exceeded that in group II, particularly in left parietal (107.6%±9.8% vs 84.1%±12.4%), left frontal (97.7%±6.7% vs 79.4%±8.9%) and left temporal areas (99.7%±7.4% vs 84.9%±10.1%) and in the cingulate cortex (112.1%±9.1% vs 95.9%±10.1%, P<0.05). Cerebral activity uptake per injected dose was inversely correlated with age in 19 children of group I (r = –0.77, P<0.001). In group I, there was also an inverse correlation between age and the relative local count density in the parietal (r = –0.42 to –0.57), frontal (r = –0.48), temporal (r = –0.42 to –0.58) and occipital cortex (r = –0.44). In these cortical regions relative counts differed when subgroups of children aged 4–10 and 11–15 years were analysed. It is concluded that there are systematic differences between 4- to 15-year-old children and adults with regard to normal lCBF. Diagnostic use of perfusion agents has to consider age-adjusted normal flow maps; normal ranges should be determined separately for the age groups 4–10 and 11–15 years.

Changes in local cerebral blood flow by neuroactivation and vasoactivation in patients with impaired cognitive function

Imaging of local cerebral blood flow (ICBF) may serve as an important supplementary tool in the aetiological assessment of dementias. In early or preclinical disease, however, there are less characteristic changes in ICBF. In the present study it was investigated whether vasoactivation or neuroactivation may produce more pronounced local ICBF deficits. Local CBF was investigated by using technetium-99m hexamethylpropylene amine oxime and single-photon emission tomography (SPET) in 80 patients (50 with mild cognitive impairment and 30 with dementia of Alzheimer type (DAT), all without evidence of cerebrovascular disease) at rest (baseline) and during activation. In 31 studies patients underwent vasomotor activation with acetazolamide, while 62 studies were performed under cognitive challenge (neuroactivation by labyrinth task). Cortical activity relative to that of cerebellum increased significantly in a right temporal region and tended to increase in other cortical regions upon vasoactivation. In contrast, neuroactivation reduced cortical activity relative to that of cerebellum in several left and right temporal and in left parietal regions. Visual classification of SPET images of patients with probable DAT by three observers resulted in a reduction of the number of definitely abnormal patterns from 9/12 to 4/12 by vasoactivation and an increase from 10/18 to 15/18 by neuroactivation. Correspondingly, abnormal ratings in patients with mild cognitive dysfunction were reduced from 7/19 to 5/19 by vasoactivation and were increased from 12/2I to 18/21 by neuroactivation. In conclusion, vasoactivation does not enhance local relative perfusion deficits in patients with cognitive impairment of non-vascular aetiology, whereas neuroactivation by labyrinth task produces more pronounced local flow differences and enhances abnormal patterns in ICBF imaging.

Radioiodination of nicotine with specific activity high enough for mapping nicotinic acetylcholine receptors

A novel radiochemical method is presented to synthesize 5-[123I/125I/131I]-dl-nicotine by radioiodination of 5-bromonicotine. Radioiodination of the precursur 5-dl-bromonicotine was achieved using a copper (I)-assisted nucleophilic exchange reaction in the presence of reducing agent. The reaction conditions were optimized by varying pH, concentration of Sn(II) salt, ascorbic acid, Cu(I)chloride and reaction temperature. After purification by high-performance liquid chromatography the radiochemical purity of the product exceeded 98%, with a radiochemical yield of 55% and a specific activity ≥5 GBq/µmol. Specific binding of the iodinated nicotine was demonstrated in rat brain by autoradiography. The radioactivity from the specific structures was displaced by an excess of non-radioactive nicotine (10−3M) withKD andBmax of 13.1±7.8 nM and 22±2.7 fmol/mg protein and unspecific binding of about 40%. The in vivo distribution of 5-[131I]iodonicotine was determined in 20 female Wistar rats at various time intervals of 15 s to 90 min post injection (p.i.) by well counting and autoradiography. Brain activity peaked within 0.5 min p.i., and then showed a biexponential washout. Initially, activity within the cerebral cortex exceeded that of the cerebellum by a factor of 1.5–2.0. It was also increased in the striatum and thalamus. However, as soon as 15 min p.i. activity was almost homogeneously distributed. In conclusion, synthesis of 5-iodo-dl-nicotine (labelled with131I,125I or123I, respectively) with appropriately high specific activity for receptor studies was achieved and specific binding to nicotine receptors in rat brain was demonstrated; following intravenous injection, however, there is considerable unspecific binding, obviously due to highly flow-dependent tissue retention.

Novel preparation of (R,R)bromo-3-quinuclidinylbenzilate (Br-QNB), a precursor for the synthesis of (R,R)[123I]iodo-QNB

Radioiodinated QNB (3-quinuclidinylbenzilate) (IV) is a potential SPET-ligand with high affinity muscarinic receptor binding. The synthesis of the precursor BrQNB (III) ((R)-(-)-azabicyclo[2. 2. 2]oct-3-yl-(R)-(+)-α-hydroxy-α-(4-bromophenyl)-α-phenylacetate) described previously was modified. Radiolabelling with iodine-123 was achieved using a copper(I) assisted nucleophilic exchange reaction resulting in high specific activity (80 GBq/μmol) and an overall yield of 56 %.

Relative Tc-99m-ECD Brain Uptake under Baseline Conditions and after Acetazolamide

This study deals with the question whether changes in brain activity uptake produced by vasoactivation differ for control subjects and patients with cerebrovascular disease (CVD). 9 subjects without and 9 patients with CVD underwent Tc-99m-ECD SPET under baseline conditions and after acetazolamide (ACZ). Ratio Q (relative cerebral activity uptake [cts/MBq] at vasoactivation and baseline) differed significantly between control subjects (1.12 ± 0.07) and CVD-patients (0.92 ± 0.03; p = 0.019), especially in patients with bilateral CVD or disseminated infarctions (n = 4) (0.86 ± 0.02; p< 0.01). In conclution, the hemodynamic relevance of CVD can be evaluated using Tc-99m-ECD SPET with ACZ, even in absence of local perfusion deficits.

Attenuation Correction in Cardiac SPET Using Two Gd-153 Line Sources — First Clinical Results

The aim of the study was to assess the benefit of simultaneous transmission and emission imaging using two Gd-153 line sources (ADAC Vertex, Vantage system). 35 patients without evidence of cardiac disease and 10 patients with posterolateral wall infarctions under-went SPET with and without attenuation correction after administration of 400 MBq Tc-99m-Tetrofosmin. The non-uniformity of the mean count profile in polar maps decreased in normal subjects significantly (range in non-corrected studies: 35.8 ± 10.8%, in attenuation corrected studies: 20.9 ± 3,3%). In patients with CAD, extent and severity of defects were more clearly represented.

Neuroactivation and Vasoactivation Studies in Patients with Impaired Cognitive Function Using Tc-99m-HMPAO-SPECT

Early stages of dementia of Alzheimer type (DAT) often fail to show characteristic patterns of local cerebral blood flow (lCBF). The present study deals with the question whether characteristic lCBF deficits can be produced or enhanced by activation. 22 patients underwent vasomotor activation by 500 mg acetazolamide and 33 patients cognitive activation by labyrinth task prior to 500 MBq Tc-HMPAO administration. According to visual scoring vasomotor activation decreased the fraction of patients with abnormal patterns from 16/22 (73 %) to 7/22 (32 %.) In contrast, neuroactivation increased the number of definitely abnormal patient studies from 19 (58 %) to 27 (82 %) out of 33 studies.