-ages 21 to 55 (Table 1) - were included in this study. All subjects had a personal interview, gave written consent and filled out a health questionnaire before the study. Exclusion criteria included pregnancy, breast feeding, history of head trauma, neurologic, psychiatric or metabolic disorders, and previous consumption of psychotropic drugs or other drugs with potential effect on the central nervous system.

Table 1.

During the personal interview the health questionnaire was completed and the subjects were informed of the purposes of the study and the methodology that was going to be used. In addition, they were informed about risks and radiation exposure during the study.

Following this, their hearing was tested (pure tone audiogram and speech discrimination) in a sound proof room. In addition, Carhart tone decay (Carhart 1957) and loudness intolerance were tested at 2 KHz. Exclusion criteria included abnormal audiogram, positive tone decay and loudness intolerance. The purpose of this evaluation was to establish that the subjects could not only hear a pure tone at 2 KHz, but that they could hear it comfortably and without tone decay.

Ten minutes prior to testing, the volunteers were premedicated with 500 mg oral potassium perchlorate and their right antecubital vein was canulated. In a sound proof, dimmed light room a pure tone was delivered at 50 dB above threshold during two minutes in the left ear by means of A G16 Grason-Stadler audiometer with head phones. Simultaneously 25mCi (925 mBq) of Tc99m - hexametyl-propylenamine-oxime (HMPAO) (Ceretec; Nycomed Amersham plc, Amersham, England) were injected intravenously with bolus technique. The subjects were instructed to concentrate on listening to the sound delivered through the headphones and to sit as motionless as possible. At the end of the two-minute period the volunteers were asked to confirm that they had heard the tone during the whole duration of the test. Sixty to ninety minutes after the injection, the neuroSPECT images were gathered on a double head Siemens - ECAM, with LEHR collimators (Mena 2004).

NeuroSPECT Image Processing (Mena 2004).

The acquisition is tridimensionally reconstructed by back projection and a Butterworth filter 4.25 is used. Non-useful information was excluded by means of an elliptic mask. We performed oblique reorientation for transaxial, coronal and sagital planes with a volume zoom of 35%. The reconstructed tridimensional raw images are transferred in an Interfile format to a personal 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 brain for cortical and also for basal ganglia analysis. The results are normalized to the maximum in the brain and displayed by means of a color scale that defines as normal the values between a range of 72% ± 5 in gray color; values above the normal mean, in red, pink and white color for values 2, 3 and 4 standard deviations above the normal mean; values below 60% (larger than 2 standard deviations below normal mean) expressed in light blue, 55% of maximum in dark blue and below 50% in green representing 2, 3 and 4 standard deviations below the normal mean.

b) Volume Normalization

We use the technique of Talairach (Mena 2004) (NEUROGAM, SEGAMI Corp. Maryland USA) for volume normalization. We reorient the tridimensional volume of the brain using standard procedure for the Neurogam software. 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 normal data bases, corrected also volumetrically, of young normal individuals aged 18 to 45 years and also for adults > 45 years. In this tridimensional image, we define a new color scale that represents in red, pink and white color values 2, 3 and 4 standard deviations above the normal mean respectively. Values below 60% (larger than 2 standard deviations below normal mean) are expressed in color light blue, 55% of maximum in color dark blue and below 50% in color green, corresponding to 2, 3 and 4 standard deviations below the normal mean respectively. (Segami Corp., Maryland, USA).

In order to define with high reproducibility the exact localization of areas of hyperperfusion observed in our patient with hallucinations and their normal controls, we produced a template of 11 areas of Brodmann in each cortical hemisphere 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 Brodmann areas are projected automatically by the computer on the 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%. Fig. 6.

Analysis of Basal Ganglia Uptake of Tc99m HMPAO.

The same acquisitions used to analyze cortical uptake distribution of HMPAO Tc99m 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 (Mena 2004) (attenuation coefficient µ=0.09cm-1). Uptake in the basal Ganglia was normalized to maximal uptake in the brain, images were displayed with the ± 2 Standard Deviations color scale and later on compared against the matched normal database, expressing the results in standard deviations above and below the normal mean.

Statistical analysis

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 region of interest (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 standard deviations of this sample. We considered that the absolute SD was a continuous variable, and therefore we applied an unpaired Student t test for the intracomparison of pairs of ipsilateral ROIs in each study group. Note: The interpreter was unaware of what volunteer or which ear was being evaluated.

B. Testing of a patient.

Clinical history.

70 year old right handed female who consulted in January 2004.
She had normal hearing (documented with audiograms in September 1999 - (Audiogram Figure 1) until October 1999 when she developed right sided profound sensorineural hearing loss (Audiogram Figure 2) associated with vestibular symptoms. Her vestibular symptoms gradually subsided but her hearing did not recover. In November 2003 she developed sudden left sided profound sensorineural hearing loss (Audiogram Figure 3) from which she did not recover. Her loss was such that hearing aids did not help her.

Audiogram Figures:

She underwent at that time complete hematologic workup which was negative. Imagenologic evaluation included Chest X rays, CAT scan (brain and mastoids) that were normal. Magnetic resonance imaging (with gadolinium) revealed only a small lacunar lesion in the head of the left caudate nucleus.

The patient had been otherwise healthy. She had had a hysterectomy. She had no thyroid, hematologic, immunologic, allergic, metabolic, or psychiatric (personal or familial) history, and was taking no medications. She had no otologic history of infection, trauma, noise or ototoxic drug exposure.

Following her second episode of hearing loss she started to hear familiar songs and, occasionally, familiar voices.

After a complete standard cochlear implant preoperative evaluation, she underwent a successful right sided cochlear implantation (Nucleus 24 Contour device) on 12 March 2004.

Her pure tones are currently normal (Audiogram Figure 4) and she is in the rehabilitation process of cochlear implantation.

The cochlear implant has not changed her listening to familiar music.

A SPECT examination was conducted with intravenous injection of Tc 99m HMPAO while she was having the sensation of listening a traditional and well-known local song entitled "Caballito Blanco."

The SPECT study was conducted in the same manner as in the 4 volunteers, but without external auditory stimulation.