We studied a cohort of 44 patients with clinical diagnosis of ABD according to DSM IV criteria. We established the following inclusion criteria: absence of psychiatric comorbidity in axis I (Unipolar depression, schizophrenia, attentional deficit and organic states among others), absence of neurological comorbidity, evolution of a period of at least six months by a clinical psychiatrist and treatment with psychopharmacological drugs for a period shorter (less) than one year. The total cohort study consisted of two groups of 22 patients each differente only on the age of presentation. We distinguished a group of early onset (mean age = 15.1 years; distribution by sex 41% males, 59% females) and a second group of late onset (mean age = 38.4 years, distribution by sex 36% males, 64% females). There was no difference in the distribution by sex (p > 0.05). There was, however, a statistically significant difference in the distribution by age (p < 0.05). The patients studied corresponded clinically to bipolar disorder type I and II. Here, the clinical status of the patient at the moment of neuroSPECT was Eutimia, namely their animic state was preserved. Clinical analysis of this cohort was performed by two clinical psychiatrists. Quantitative imagenological analysis and also the data analysis were performed by two blinded investigators with respect to the identification of patients and its characteristics.
Preparation of the Patient
Patient discontinued psychotropic medication at least 5 days before the performance of the NeuroSPECT test and 24 hours before, discontinued also consumption of tea, coffee, chocolate and cola beverages. Besides these limitations, the NeuroSPECT examination is performed under normal dietary conditions.
Contraindication of NeuroSPECT. Test can not be performed in pregnant women or in women suspected of the possibility of pregnancy.
Injection of the radiopharmaceutical
30mCi of HMPAO Tc-99m (Ceretec Amersham) (1110 mBq) in basal conditions are injected intravenously with the patient in dorsal decubitus in a room with ambient noise and light under control, the patient has the eyes opened and the injection is performed into an antecubital vein that is cannulated 10 minutes before. The intravenous injection is given in an approximate volume of 2 ml. followed by a bolus of normal saline of 10 ml. 60 to 90 minutes after the injection, the NeuroSPECT images are gathered.
The patient lies on whole body table with the head fixed in a head holder of special design with pillows under his knees, arms at the side of his trunk and the head is supported with a Velcro band on the forehead and chin.
For the SPECT acquisition we use a NeuroSPECT Sophy DSX (SMV, Ohio, USA) system with rectangular head and Ultra High Resolution collimator; we use an energy window 140 Kev with a window width of 20%. The matrix is 64 x 64 with a circular orbit and Step&Shoot motion with 64 steps and 360 degrees rotation. The time of acquisition per projection is 30 seconds with a zoom factor of 1.66 and at the end of acquisition we verify the possibility of a motion artifact in a Cine mode and the Sinogram will demonstrate the existence of patient motion. If there is patient motion, the acquisition is repeated without the necessity of reinjecting the patient.
NeuroSPECT Image Processing
The acquisition is tridimensionally reconstructed by back projection by means of a Butterworth filter 4.25, delimiting non-useful information by means of an elliptic ROI. We perform oblique reorientation for transaxial, coronal, and sagittal planes with a volume zoom of 35%.
The reconstructed tridimensional raw images are transferred in a M03 format to a PC computer in order to reprocess, quantify and normalize their volume.
a) Normalization of HMPAO brain uptake.
The computer performs an analysis of voxel by voxel brain uptake of HMPAO, the results are normalized and expressed as percentage of maximal uptake observed in the cerebellum for cortica analysis and in the brain for basal ganglia analysis, the results are displayed by means of a color scale that defines as normal values the ones observed between a range of 72% + 5 in red color, values above the normal mean, in silver color values above 82%, values below 60% (larger than 2 standard deviations below normal mean) expressed in color yellow, 50% of maximum in color green and below 40% in color blue.
We use the technique of Talairach (Arcila et al Alasbimn, Lima 1997) (NEUROGAM, SEGAMI Corp. Maryland USA). We reorient the tridimensional volume of the brain defining a line that fits the inferior pole of the occipital lobe and the inferior edge of the frontal lobe; this line is automatically rendered horizontal. We correct for lateral deviations defining a line above the interhemisphere fissure and automatically orienting this line in the vertical plane. In this reoriented image we define the intermediate level of the pons and anterior plane of the temporal lobes. We limit the volume of analysis in the lateral planes, superior and inferior planes of the brain. With this information, the Talairach technique renders the brain volume into a normalized volume and allows therefore, a voxel by voxel comparison of the HMPAO uptake in the brain cortex with a normal data base, corrected also volumetrically, for normal children age 6 to 15 years and young normal individuals at the age of 18 to 45 yeas. In this tridimensional image, we define a new color scale that represents in color red values above the normal mean and two standard deviations above the normal mean in color Silver, all values below the normal mean, in color green and all values below two standard deviations below the normal mean, in color BLUE. We define, therefore, areas of abnormal hypoperfusion that have 95% of probability of being hypoperfused and demonstrated in color BLUE and areas of hyperperfusion in color SILVER that have 95% probability of being hyperperfused in comparison with the normal database (Segami Corp., Maryland, USA).
The intraobserver reproducibility of these measurements was reported at the Alasbimn Meeting in Lima, Peru, 1997 and has a mean of reproducibility of 3.6 mm. that is considered acceptable for this type of technology.
In order to define with high reproducibility the exact localization of areas of hypoperfusion observed in Major Depression and of hyperperfusion observed in Bipolar Disorders, we produced a template of 11 areas of Brodmann in each cortical hemisphere that are involved with behavioral activities by means of the program CORELDRAW 8. We used the Brodmann areas as reference for clinical and experimental functional cerebral and pathological reported information. All these behavioral Brodmann areas are projected automatically by the computer on the anterior, left and right lateral and both para-sagittal images of the three dimensional images of the brain. The projection of this template is automatic and therefore the reproducibility of the results is 100%.
Analysis of Basal Ganglia Uptake of Tc99m HMPAO. The same acquisitions used for analysis cortical distribution of HMPAO Tc99m uptake were used for further evaluation of basal Ganglia uptake. For this purpose Images were corrected in first place for attenuation by Chang's first order method (attenuation coefficient µ=0.09cm-1). Latter on uptake was normalized to maximal uptake in the brain and images were displayed with the + 2 Standard Deviations color scale and later on compared against the matched normal database and results expressed in standard deviations above and below the normal mean.
Quantification of extension of hypoperfusion in each cortical Brodmann area. By consensus of two of the investigators, we estimated the percentage of sub-regions o hypoperfusion demonstrated by means of blue color in the colorimetric scale.
A voxel by voxel comparative analysis with a normal age matched control group was performed and cortical perfusion values were expressed as Standard Deviation (SD) above or below the normal mean for this age group. ROIs were defined by cortical Brodmann Areas and our system determined the maximal perfusion level in each ROI. We considered as abnormally increased perfusion only with maximal perfusion values above 2 SD of the normal mean perfusion. For each of 15 ROIs studied, we calculated the mean of the SDs of this sample. We considered that the absolute SD was a continuous variable, and therefore we applied an unpaired Student t test for the intracomparisson of pairs of ipsilateral ROIs in each study group.