Contribution of single photon emission computed tomography to the differential diagnosis of dementia in a memory clinic.

To evaluate the contribution of single photon emission computed tomography (SPECT) to the differential diagnosis of dementia, we studied 48 consecutive patients (median age: 63) with a degenerative or vascular dementia, a 99mTc-HMPAO SPECT imaging, and a diagnostic confirmation (autopsy or genetic mutation). The SPECT scans were visually rated by two nuclear medicine physicians (first blinded to the clinical data, then with the data). Comparisons between clinical diagnoses and/or SPECT imaging and neuropathology were performed. At the time of SPECT was performed, the clinical diagnosis of Alzheimer's disease (AD) sensitivity was 83%, specificity was 76%, and diagnostic accuracy was 79%. The blinded SPECT sensitivity was 57%, specificity 92%, and diagnostic accuracy 75%. The SPECT associated with clinical data sensitivity was 65%, specificity 84%, and accuracy 75%. The clinical diagnosis of frontotemporal-lobar degeneration (FTLD), progressive supranuclear palsy (PSP), and corticobasal degeneration syndrome (CBDs) sensitivity was 83%, specificity 87%, and accuracy 85%. The blinded SPECT sensitivity was 50%, specificity 97%, and accuracy 79%. The SPECT associated with clinical data sensitivity was 61%, specificity was 93%, and accuracy 81%. Whenever the blinded SPECT interpretation agreed with the clinical diagnosis of AD and FTLD/PSP/CBDs, the condition was confirmed by neuropathological assessment in all cases. Compared with clinical diagnosis alone, SPECT imaging improved the specificity of the etiological diagnosis in degenerative dementia, although its sensitivity was not as good as that of clinical diagnosis. For AD and FTLD/PSP/CBDs, agreement between the clinical and SPECT-based diagnoses was always confirmed by neuropathological assessment.

Pulmonary perfusion scintigraphy: a tool to detect the presence of pulmonary artery involvement in Takayasu's arteritis.

OBJECTIVE: Takayasu arteritis (TA) is a large-vessel vasculitis that can also involve pulmonary arteries. The aim of this study was to evaluate the frequency of pulmonary artery involvement in TA patients using pulmonary perfusion scintigraphy (PPS) and to determine the characteristics of patients with pulmonary artery involvement. METHODS: Twenty-one patients classified as having TA underwent PPS. PPS positivity was defined as the presence of perfusion defects with normal ventilation. TA diagnosis was assessed using American College of Rheumatology (ACR) and/or Ishikawa's modified criteria. RESULTS: Twenty-one patients (median age 36 years [range; 21-78]; 18 females) were analyzed. PPS was positive in 12 (57%) patients. Pulmonary symptoms were present in 4/12 patients with positive PPS, but none in patients with negative PPS. Among the 12 patients with positive PPS, eight patients (67%) were asymptomatic with regard to pulmonary involvement. No difference was noted between patients with positive and negative PPS with respect to general characteristics, vascular involvement, biological parameters or treatment regimen. PPS sensitivity was 100%, specificity at 53% and predictive negative value at 100% in patients with TA relative to the presence of pulmonary symptoms. CONCLUSION: Although frequent, pulmonary artery involvement in TA is often asymptomatic. Its systematic detection by PPS could be valuable in the diagnosis of TA.

Pre-therapy 18F-FDG PET quantitative parameters help in predicting the response to radioimmunotherapy in non-Hodgkin lymphoma.

PURPOSE: Radioimmunotherapy (RIT) is a new treatment option for patients with non-Hodgkin lymphoma (NHL). Response to RIT currently remains difficult to predict using conventional prognostic factors and could be refined using functional imaging. The goal of this work is to evaluate the value of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in predicting response to Yttrium 90-labeled monoclonal antibodies for patients with NHL. METHODS: Thirty-five patients with NHL who had undergone (18)F-FDG PET prior to RIT with either (90)Y-ibritumomab tiuxetan (group A; n = 17) or (90)Y-epratuzumab tetraxetan (group B; n = 18) were included in this retrospective study. Four functional criteria were determined for each tumour lesion in a given patient: maximum and mean standard uptake values (SUVmax and SUVmean), functional lesion volume (LVol) and total lesion glycolysis (TLG, product of the volume and the SUVmean). For each patient, we determined highest SUVmax and SUVmean, cumulative TLG (TLGcum) and sum of all LVol (TVol) and compared their predictive value on response (complete or partial response according to IWC) to RIT with those of conventional prognostic factors in group A and B. RESULTS: A total of 154 lesions were analysed. Nineteen patients (54%) responded to RIT according to IWC. In group A, response rate was 54, 75 and 75% in patients with a SUV max <20 g/ml, a TVol <100 ml and a TLGcum <1060 g, respectively while no patient above these thresholds responded (p < 0.005). In group B, the response rate was 93% for with SUVmax <15 g/ml while no patient above this threshold responded. With TLGcum below 1,360 g, 100% of the patient responded, compared with 37% of patients whose TLGcum was above this threshold (p < 0.05). By contrast, conventional prognostic factors failed to predict response. CONCLUSIONS: Our preliminary results indicate that pre-therapy (18)F-FDG PET functional parameters such as SUVmax and TLG may help predicting more accurately response to single agent Y90 based RIT.

Fetal cortical activation to sound at 33 weeks of gestation: a functional MRI study.

Hearing already functions before birth, but little is known about the neural basis of fetal life experiences. Recent imaging studies have validated the use of functional magnetic resonance imaging (fMRI) in pregnant women at 38-weeks of gestation. The aim of the present study was to examine fetal brain activation to sound, using fMRI at the beginning of the third trimester of pregnancy. 6 pregnant women between 28- and 34-weeks of gestation were scanned using a magnetic strength of 1.5 T, with an auditory stimulus applied to their abdomen. 3 fetuses with a gestational age of 33 weeks, showed significant activation to sound in the left temporal lobe, measured using a new data-driven approach (Independent Component Analysis for fMRI time series). Only 2 of these fetuses showed left temporal activation, when the standard voxel-wise analysis method was used (p=0.007; p=0.001). Moreover, motion parameters added as predictors of the General Linear Model confirmed that motion cannot account for the signal variance in the fetal temporal cortex (p=0.01). Comparison between the statistical maps obtained from MRI scans of the fetuses with those obtained from adults, made it possible to confirm our hypothesis, that there is brain activation in the primary auditory cortex in response to sound. Measurement of the fetal hemodynamic response revealed an average fMRI signal change of +3.5%. This study shows that it is possible to use fMRI to detect early fetal brain function, but also confirms that sound processing occurs beyond the reflexive sub-cortical level, at the beginning of the third trimester of pregnancy.

99mTc-MIBI brain SPECT as an indicator of the chemotherapy response of recurrent, primary brain tumors.

BACKGROUND: Malignant brain tumors carry a pejorative prognosis and necessitate aggressive therapy. Chemotherapy can be used in cases of tumor recurrence. With limited response rate and potential toxicity to chemotherapeutic treatment in patients with recurrent glioma, reliable response assessment is essential. AIM: To define the place of 99mTc hexakis 2-methoxyisobutylisonitrile (99mTc-MIBI) Single Positron Emission Computed Tomography (SPECT) in monitoring chemotherapy response in recurrent primary brain tumors. METHODS: In a retrospective analysis, thirty patients were investigated with MIBI SPECT. Imaging was performed 1h after the intravenous injection of 555 MBq of 99mTc-MIBI using a dedicated SPECT system. A MIBI uptake index (UI) was computed as the ratio of counts in the lesion to those in contralateral region. For all patients, we compared changes over time in UI with MRI and clinical data. RESULTS: The changes in UI agreed well with the clinical and MRI-based assessments in 97% of cases. In 44% of these cases, the scintigraphic response appeared before the MRI response. In instances of treatment failure or rebound, the concordance between scintigraphy and MRI was 52%, and the scintigraphic response appeared before the MRI response in 48% of cases. CONCLUSION: This study confirms our previous results obtained on a short series of patients with recurrent glioma, concerning the usefulness of MIBI SPECT in prediction of chemotherapy response. Moreover, in cases of tumor progression, we show that MIBI SPECT is an earlier indicator of escape from chemotherapy, an average 4 months before MRI changes.

Self awareness and speech processing: an fMRI study.

Language production and perception imply motor system recruitment. Therefore, language should obey the theory of shared motor representation between self and other, by means of mirror-like systems. These mirror-like systems (referring to single-unit recordings in animals) show the property to be recruited both when accomplishing and when perceiving a goal-directed action, whatever the sensory modality may be. This hypothesis supposes that a neural network for self-awareness is involved to distinguish speech production from speech listening. We used fMRI to test this assumption in 12 healthy subjects, who performed two different block-design experiments. The first experiment showed involvement of a lateral mirror-like network in speech listening, including ventral premotor cortex, superior temporal sulcus and the inferior parietal lobule (IPL). The activity of this mirror-like network is associated with the perception of an intelligible speech. The second experiment looked at a self-awareness network. It showed involvement of a medial resting-state network, including the medial parietal and medial prefrontal cortices, during the 'self-generated voice' condition, as opposed to passive speech listening. Our results support the fact that deactivation of this medial network, in association with modulation of the activity of the IPL (part of the mirror-like network previously described), is linked to self-awareness in speech processing. Overall, these results support the idea that self-awareness is present when distinguishing between speech production and speech listening situations, and may depend on these two different parieto-frontal networks.

Sestamibi technetium-99m brain single-photon emission computed tomography to identify recurrent glioma in adults: 201 studies.

OBJECT: In the follow-up of treated gliomas, CT and MRI can often not differentiate radionecrosis from recurrent tumor. The aim of this study was to assess the interest of functional imaging with (99m)Tc-MIBI SPECT in a large series of 201 examinations. METHOD: MIBI SPECT were performed in 81 patients treated for brain gliomas. A MIBI uptake index was computed as the ratio of counts in the lesion to counts in the controlateral region. SPECT was compared to stereotactic biopsy in 14 cases, or in the others cases to imaging evolution or clinical course at 6 months after the last tomoscintigraphy Two hundred and one tomoscintigraphies were performed. One hundred and two scans were true positive, 82 scans were true negative. Six scans were false positive (corresponding to 3 patients): 2 patients with an inflammatory reaction after radiosurgery, 1 with no explanation up to now. Eleven scans were false negative (5 patients): 1 patient with a deep peri-ventricular lesion, 2 patients with no contrast enhancement on MRI, 2 patients with a temporal tumor. The sensitivity for tumor recurrence was 90%, specificity 91.5% and accuracy 90.5%. We studied separately low and high grade glioma: sensitivity for tumor recurrence was respectively 91% and 89%, specificity 100% and 83% and accuracy 95% and 87%. MIBI SPECT allowed the diagnose of anaplasic degenerence of low grade sometimes earlier than clinical (5 cases) or MRI signs (7 cases). CONCLUSIONS: Our results confirm the usefullness of MIBI SPECT in the follow-up of treated gliomas for the differential diagnosis between radiation necrosis and tumor recurrence.

Corticobasal degeneration and Parkinson's disease assessed by HmPaO SPECT: the utility of factorial discriminant analysis.

The diagnosis of corticobasal degeneration (CBD) is difficult despite the existence of some typical clinical features. Single photon emission computerized tomography (SPECT) in CBD presents an original pattern (with asymmetric hypoperfusion in pre- and retrorolandic regions) that could facilitate the differential diagnosis of CBD relative to the other degenerative parkinsonian syndromes. The objective of our study was to compare the regional cerebral blood flow measurements studied by SPECT in both CBD and Parkinson's disease (PD) using a multivariate procedure. Twenty-one patients with probable CBD and 20 patients with probable PD underwent brain (99m)Tc HmPaO SPECT. We used factorial discriminant analysis (FDA) to study the relative fixation of 26 regions of interest (ROIs) drawn on two transverse slices, together with the asymmetry indexes of 13 pairs of ROIs. FDA performed using the full set of parameters classified all the patients correctly. In order to classify the patients more easily, a predictive score using a selection of parameters was established. The most discriminating ROIs were the temporoinsular, temporoparietal, and frontal medial regions. We believe that this semiautomatic classification may be a precious tool for reinforcing the current clinical differential diagnosis of CBD and PD.

Cognitive and SPECT characteristics predict progression of Parkinson's disease in newly diagnosed patients.

OBJECTIVE: To identify features in cognitive functioning and regional cerebral blood flow (rCBF) in newly diagnosed Parkinson's disease (PD) patients and to determine whether these factors are able to predict the progression of the disease in general and the development of cognitive decline in particular. METHODS: 50 previously treatment-naive PD patients participated in the study. Cognitive assessment and SPECT were performed twice: at the time of diagnosis and then 3 years later. Six patients died or refused to continue. The Mattis dementia rating scale, the WAIS-R digit span test, a word list learning/recall test, a word fluency task and the Stroop word-colour test were used to assess cognitive function. rCBF was measured in 10 pairs of regions of interest. Principal component analysis of the data from the final examination was used to determine which variables allowed the formation of patient subgroups. Thereafter, factorial discriminant analysis (FDA) was performed in order to obtain a predictive model of these final classes. RESULTS: A stepwise procedure enabled the identification of 3 clusters (26, 16 and 2 patients). As the patients in the smallest cluster met the criteria for dementia at the final examination, they were discarded from further analyses. All the cognitive variables contributed to the constitution of the two other clusters. Age, educational level and all the rCBF parameters also contributed but to a lesser extent. Comparison of these groups showed reduced overall cognitive efficiency and an exacerbated subcorticofrontal syndrome in the 16-patient cluster. FDA showed that the best predictive model for the final classes was based on 7 variables: educational level, semantic and alternating word fluency, Stroop interference index and the right medial frontal, left parietal and left lenticular nucleus rCBF findings. CONCLUSION: Even though both cognitive and rCBF parameters help predict the progression of newly diagnosed PD patients and bearing in mind the limitations of the SPECT method used here, it appears that the contribution of cognitive assessment is greater than that of rCBF measurement.

Technetium-99m sestamibi brain SPECT in the follow-up of glioma for evaluation of response to chemotherapy: first results.

The initial treatment of high-grade glioma often consists of surgery and radiation therapy. Chemotherapy is used in cases of recurrence or after incomplete surgery. Because of the many potential serious side-effects of chemotherapy, early tumour response evaluation is necessary to enable clinicians to adapt the treatment. However, response monitoring with computed tomography (CT) or magnetic resonance imaging (MRI) is often difficult. The aim of this study was to assess the value of repeated technetium-99m methoxyisobutylisonitrile ((99m)Tc-MIBI) single-photon emission computerised tomography (SPECT) for this purpose. Fifteen patients with malignant glioma were investigated with MIBI SPECT. Imaging was performed 1 h after the intravenous injection of 555 MBq of (99m)Tc-MIBI, using a dedicated SPECT system (Tomomatic 564, Medimatic, Denmark). Overall, 57 investigations were performed. A MIBI uptake index was computed as the ratio of counts in the lesion to those in the contralateral region. Previous study had shown a cut-off value of 2.0 to be appropriate. SPECT indices were compared with neurological evaluation, CT or MRI. This assessment was performed every 4 months during and after the treatment. Six patients showed an increased MIBI index associated with clinical or radiological progression of disease during chemotherapy. After an initial response to therapy, three patients showed an increased MIBI index despite chemotherapy, demonstrating secondary resistance to therapy. Six patients showed a decreased MIBI index, demonstrating a good response to therapy. The first nine patients died shortly after the last SPECT scan (average duration of survival, 4 months). The therapeutic protocol was modified in six cases, but successfully so in only two. In some cases, tumour progression was diagnosed earlier with SPECT than on the basis of clinical or MRI signs. Early response or resistance to chemotherapy is detectable by(99m)Tc-MIBI SPECT. Therefore this functional imaging modality could be considered as a valuable tool to permit effective adaptation of the therapeutic regimen in patients treated for recurrent high-grade glioma.

SPECT imaging, clinical features, and cognition before and after low doses of amisulpride in schizophrenic patients with the deficit syndrome.

The aim of the study was to examine the action of low-dose amisulpride (100 mg/d), an atypical antipsychotic from the benzamide class with a high affinity for the D2 and D3 dopamine receptors, given for 4 weeks in 19 schizophrenic patients with the deficit syndrome, in terms of clinical response, modifications in their cognitive performance and changes in brain perfusion values. A secondary objective was to distinguish between primary and secondary deficit, according to Carpenter's definition. Both efficacy and a relatively low rate of side effects of low-dose amisulpride in the deficit forms of schizophrenia were found as expected from earlier placebo-controlled studies. Our study found significant changes in the cerebral blood flow, before and after treatment, more marked in the frontal area and particularly in the dorso-lateral frontal area. A significant improvement of cognitive function was found after treatment, without a link to any particular changes in a loco-regional perfusion value. Finally, a distinction between primary and secondary deficit showed a higher percentage of clinical improvement in the patients with a secondary deficit. The psychometric and cerebral perfusion changes were no different in the two groups.

Regional cerebral blood flow in deficit/nondeficit types of schizophrenia according to SDS criteria.

A relationship between "hypofrontality" and a negative form of schizophrenia is commonly found. The Schedule for the Deficit Syndrome (SDS) provides specific criteria for assessing the presence of negative symptoms, their duration and whether the symptoms are primary or secondary. The purpose of our study was to compare the regional cerebral blood flow (rCBF) at rest, in 62 deficit and nondeficit schizophrenic patients, according to the SDS criteria (French version). The deficit patients in our population were comparable to those described in the literature (stability of their negative symptoms with time, poor premorbid adjustment, duration of the illness, age at the first episode, etc.). No difference was found in the locoregional perfusion with respect to the DSM-III-R type of schizophrenia, the sex or the type of treatment received. The patients with a deficit form of schizophrenia showed a significant bilateral reduction in single photon emission computed tomography (SPECT) perfusion in the right frontodorsolateral cortex (P=.0105) and the left frontodorsolateral cortex (P=.0004) compared with the nondeficit schizophrenic patients. The contribution of SDS seems to be helpful in distinguishing between significant cerebral characteristics in deficit schizophrenics, as defined by Carpenter. These results suggest a decrease in prefrontal perfusion at rest, which corresponds with neuropsychological data.

Levodopa and bromocriptine in hypoxic brain injury.

BACKGROUND: Postanoxic encephalopathy is frequent in patients presenting with abrupt cardiac arrest or respiratory failure. Little is known about the effectiveness of oral medications on the cognitive and motor consequences. OBJECTIVE: To present data suggesting partial improvement after administration of levodopa/benserazide. METHODS: After observing partial benefit in one case, each patient admitted to rehabilitation following brain anoxia was systematically treated with levodopa/benserazide (200/50 to 400/100 mg/day), then bromocriptine (15 mg/day). RESULTS: In the first patient, brain anoxia was severe, with secondary agitation, quadriparesis, involuntary movements, inattention and communication disorders. Introduction of levodopa/benserazide resulted in reduction of agitation and involuntary movements and improvement of communication, thus facilitating care and rehabilitation efforts. A weaning test resulted in rapid worsening. The four following patients also presented with anoxia of variable severity. Marked improvement was observed in case 2, presenting with agitation, loss of orientation, amnesia, postural disorders, involuntary movements and dysphagia, with a withdrawal test resulting in immediate re-enhancement of symptoms. Modest improvement was observed in patient 3, who had hypokinesia, rigidity, adynamia, impaired attention, and reduced verbal fluency. Patient 4 presented with memory disorders without motor difficulties: mild improvement was observed in daily life and memory tests. In patient 5 who also presented with severe memory disorders, the benefit was absent. In each case, bromocriptine was introduced 3-4 weeks following levodopa, but without additive effect. Both treatments could be interrupted after a few months, without worsening. CONCLUSIONS: Levodopa and benserazide can be of benefit in the few months following brain anoxia, especially on some of the motor disorders and apathy, but the benefit is inconstant and modest on memory disorders. Anoxia could alter dopaminergic mesencephalic systems, which activate the striatal and mediobasal frontal cortex, and these disorders could be partially reversible by medical treatment.