B Garada

Boston Children's Hospital, Boston, MA, United States

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Publications (27)91.54 Total impact

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    Synapse 12/1998; 22(3):239 - 246. · 2.31 Impact Factor
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    ABSTRACT: The study was conducted to determine the association between dual-isotope single-photon emission computerized tomography (SPECT) scanning and histopathological findings of tumor recurrence and survival in patients treated with high-dose radiotherapy for glioblastoma multiforme. Studies in which SPECT with 201Tl and 99mTc-hexamethypropyleneamine oxime (HMPAO) were used were performed 1 day before reoperation in 47 patients with glioblastoma multiforme who had previously been treated by surgery and high-dose radiotherapy. Maximum uptake of 201Tl in the lesion was expressed as a ratio to that in the contralateral scalp, and uptake of 99mTc-HMPAO was expressed as a ratio to that in the cerebellar cortex. Patients were stratified into groups based on the maximum radioisotope uptake values in their tumor beds. The significance of differences in patient gender, histological characteristics of tissue at reoperation, and SPECT uptake group with respect to 1-year survival was elucidated by using the chi-square statistic. Comparisons of patient ages and time to tumor recurrence as functions of 1-year survival were made using the t-test. Survival data at 1 year were presented according to the Kaplan-Meier method, and the significance of potential differences was evaluated using the log-rank method. The effects of different variables (tumor type, time to recurrence, and SPECT grouping) on long-term survival were evaluated using Cox proportional models that controlled for age and gender. All patients in Group I (201Tl ratio < 2 and 99mTc-HMPAO ratio < 0.5) showed radiation changes in their biopsy specimens: they had an 83.3% 1-year survival rate. Group II patients (201Tl ratio < 2 and 99mTc-HMPAO ratio of > or = 0.5 or 201Tl ratio between 2 and 3.5 regardless of 99mTc-HMPAO ratio) had predominantly infiltrating tumor (66.6%); they had a 29.2% 1-year survival rate. Almost all of the patients in Group III (201Tl ratio > 3.5 and 99mTc-HMPAO ratio > or = 0.5) had solid tumor (88.2%) and they had a 6.7% 1-year survival rate. Histological data were associated with 1-year survival (p < 0.01): however, SPECT grouping was more closely associated with 1-year survival (p < 0.001) and was the only variable significantly associated with long-term survival (p < 0.005). Dual-isotope SPECT data correlate with histopathological findings made at reoperation and with survival in patients with malignant gliomas after surgical and high-dose radiation therapy.
    Journal of Neurosurgery 07/1998; 89(1):60-8. · 3.15 Impact Factor
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    ABSTRACT: Lyme encephalopathy (LE) presents with subtle neuropsychiatric symptoms months to years after onset of infection with Borrelia burgdorferi. Brain magnetic resonance images are usually normal. We asked whether quantitative single photon emission computed tomography (SPECT) is a useful method to diagnose LE, to measure the response to antibiotic therapy, and to determine its neuroanatomic basis. In 13 patients with objective evidence of LE, SPECT demonstrated reduced cerebral perfusion (mean perfusion defect index [PDI] = 255), particularly in frontal subcortical and cortical regions. Six months after treatment with 1 month of intravenous ceftriaxone, perfusion significantly improved in all 13 patients (mean PDI = 188). In nine patients with neuropsychiatric symptoms following Lyme disease, but without objective abnormalities (e.g., possible LE), perfusion was similar to that of the treated LE group (mean PDI = 198); six possible LE patients (67%) had already received ceftriaxone prior to our evaluation. Perfusion was significantly lower in patients with LE and possible LE than in 26 normal subjects (mean PDI = 136), but 4 normal subjects (15%) had low perfusion in the LE range. We conclude that LE patients have hypoperfusion of frontal subcortical and cortical structures that is partially reversed after ceftriaxone therapy. However, SPECT cannot be used alone to diagnose LE or determine the presence of active CNS infection.
    Neurology 01/1998; 49(6):1661-70. · 8.30 Impact Factor
  • B Garada, RA Klufas, RB Schwartz
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    ABSTRACT: Closed head injury can be associated with significant neurologic dysfunction. Neuroimaging in this condition consists of conventional techniques such as computed tomography (CT) and magnetic resonance imaging (MR), and functional imaging studies such as single photon emission computerized tomography (SPECT) and positron emission tomography (PET). Whereas CT and MR are sufficient to show the acute concomitants of head trauma such as extra-axial hematomas, contusions, and shear injury, functional brain imaging has been shown to play an important role in management of victims of closed head injury, particularly in the chronic stages. Detection of changes in regional cerebral blood flow associated with brain injury have been found to correlate better with neurological status and prognosis than abnormalities seen by CT or MRI.
    Seminars in Clinical Neuropsychiatry 08/1997; 2(3):188-195.
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    ABSTRACT: The dopamine transporter (DAT), located presynaptically on dopamine neurons, provides a marker for certain neurological diseases. In particular, the DAT is depleted in Parkinson's disease, and the extent of depletion correlates with the loss of dopamine. Herein we describe the design, synthesis, and biological evaluation of technepine, the first 99mTc-labeled SPECT imaging agent which targets the dopamine transporter in striatum. We have demonstrated that the DAT can accommodate a chelating unit attached to the 8-amine function of a tropane skeleton. Further, we have demonstrated for the first time that a molecule can be designed to carry the radionuclide 99mTc across the blood-brain barrier in sufficient quantity to obtain in vivo images of the striatum in monkeys. This advance will undoubtedly lead to the design of new receptor and transporter-mediated 99mTc agents which can label specific transporter and receptor targets in the central nervous system.
    Journal of Medicinal Chemistry 07/1997; 40(12):1835-44. · 5.61 Impact Factor
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    ABSTRACT: The acute pathophysiologic changes during hemiplegic spells and the long-term outcome of alternating hemiplegia remain obscure. In a 41-year-old male with familial alternating hemiplegia we found an increase in right frontal cerebral blood flow 3 h into a 5-h left hemiplegic episode. A repeat high-resolution brain SPECT study performed 26 h after the resolution of the left hemiplegia revealed normalization of the frontal blood flow accompanied by hyperperfusion in the right parietal lobe. An interictal SPECT scan several weeks later showed no asymmetries. Head CT and MRI scans were negative. Neuropsychologic assessment and neurologic examination revealed evidence of a diffuse disorder which predominantly involved the right hemisphere. To our knowledge, there are no previous correlative studies of serial high-resolution brain SPECT with MRI, or of detailed neuropsychologic assessment, in adult patients with such an advanced course of alternating hemiplegia of childhood.
    European Archives of Psychiatry and Clinical Neuroscience 02/1997; 247(1):35-41. · 3.36 Impact Factor
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    ABSTRACT: Explore the use of functional imaging data in radiation treatment planning of brain lesions. Compare the treatment-planning process with and without the use of functional brain imaging for clinical cases where functional studies using either single photon emission computed tomography or magnetic resonance imaging are available. A method to register functional image data with planning image studies is needed for functional treatment planning. Functional volumes are not simply connected regions. One activation study may produce many isolated functional areas. After finding the functional volumes and registering the functional information with the planning imaging data, the tools used for conventional three-dimensional treatment planning are sufficient for functional treatment planning. However, the planning system must provide dose-volume histograms for volumes of interest that consist of isolated pieces. Treatment plans that spare functional brain while providing identical target coverage can be constructed for lesions situated near the functional volume. However, the dose to other areas of the brain may be increased. Functional imaging will make determination of dose response of eloquent areas of the brain possible when combined with volumetric dose information and neuropsychological evaluation prior to and after radiation therapy. Realizing the full potential of functional imaging studies will require improved delineation of activated volumes and determination of the uncertainties in functional volume delineation. Optimization of treatment plans by minimizing dose to volumes activated during functional imaging studies should be used cautiously, because the dose to "silent," but possibly eloquent, brain may be increased.
    International Journal of Radiation OncologyBiologyPhysics 02/1997; 37(1):181-8. · 4.52 Impact Factor
  • Neurosurgery 01/1997; 41(3). · 2.53 Impact Factor
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    ABSTRACT: High resolution single photon emission computed tomography (SPECT) was used to evaluate regional cerebral blood flow (rCBF) in 14 acutely depressed elderly patients and 29 normal subjects. SPECT images of the two groups were randomized and blindly read. Foci of decreased radionuclide uptake were assessed by number and location. The total number of rCBF defects per whole brain study was significantly greater in the depressed patients than in the normal subjects. A significantly greater number of rCBF defects was found most strikingly in the lateral frontal and less prominently in the lateral and medial temporal brain regions of the depressed patients.
    Psychiatry Research 06/1996; 67(1):59-70. · 2.68 Impact Factor
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    ABSTRACT: We have initiated a study in which patients suspected of having primary gliomas are given a single intracerebral injection of the thymidine analog 5-[123I]iodo-2'-deoxyuridine ([123I]IUdR). The purpose of the study is to determine the biodistribution of the radiopharmaceutical and to calculate dose estimates to the tumor and normal tissues. A patient with a cystic glioma was injected with [123I]IUdR. Whole-body scans and brain scans were obtained at various times after injection, and blood, urine and stools were collected and assayed for radioactivity to assess its biodistribution and clearance. Scintigraphic imaging demonstrated that the distribution of radiolabeled IUdR was mainly confined to the tumor (injection site), stomach and bladder. Disappearance from the tumor site and blood clearance were delayed probably due to collection in the cystic lesion. Eighty percent of the injected dose was recovered in the urine. The pharmacokinetics of [123I]IUdR locoregionally administered to a human glioma in situ resembled those observed in a rat glioma model where administration of the radiopharmaceutical radiolabeled with the Auger electron emitter 125I was therapeutically effective.
    Journal of Nuclear Medicine 05/1996; 37(4 Suppl):19S-22S. · 5.77 Impact Factor
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    Synapse 04/1996; 22(3):239-46. · 2.31 Impact Factor
  • Neurosurgical Focus - NEUROSURG FOCUS. 01/1996; 1(3).
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    ABSTRACT: Chronic cocaine and polydrug abuse have been associated with regional abnormalities in cerebral perfusion. The authors have previously demonstrated that these abnormalities are partially reversible after drug addiction treatment with buprenorphine. This study was designed to separate the effect on cerebral perfusion of abstinence from drug use from that of buprenorphine directly. Fifteen cocaine- and heroin-dependent men were studied with 99mTc-hexamethylpropyleneamine oxime (HMPAO) brain SPECT. The men, all part of an inpatient drug abuse treatment research program, were randomly assigned after detoxification to receive placebo or either 6 or 12 mg daily buprenorphine treatment. SPECT studies were performed at baseline, after maximum dosage was reached and after tapering off the study drug. Studies were compared visually with regard to the number and location of perfusion defects by reviewers blinded to treatment assignment. Subjects receiving buprenorphine had a significant reduction in the number of defects per study between baseline and maximum buprenorphine dose as compared with those receiving placebo (decrease of 4 +/- 5.4 versus increase of 4.8 +/- 4.7, p = 0.006). These differences were dose-related. Improvement with buprenorphine was temporary, with return to baseline after tapering off. Buprenorphine treatment, and not abstinence from drug use alone, leads to improvement in regional cerebral perfusion abnormalities in chronic cocaine- and heroin-dependent men.
    Journal of Nuclear Medicine 08/1995; 36(7):1211-5. · 5.77 Impact Factor
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    ABSTRACT: To verify the utility of a volumetric estimation of Tl-201 uptake in the context of possible astrocytoma recurrence after surgery, radiotherapy plus stereotactic boost (radiosurgery/brachitherapy), we analyzed sequential Tl-201/Tc99m-HMPAO brain SPECT studies of 28 patients (18 m/10 f). These were categorized as having tumor mass recurrence (TM), infiltrating tumor cells but no definite tumor mass (IT), or radiation changes and necrosis (RCN) after stereotactic biopsy and/or craniotomy. SPECT studies were obtained with a high-resolution dedicated gamma camera (CERASPECT, Digital Scinitgraphics, Inc.) and image acquisition was performed after intravenous Tl-201 (18.5 MBq) and Tc-99m HMPAO (740 MBq). In order to include relevant information about tumor burden, a volumetric index of Tl-201 uptake was expressed in cm{sup 3} related to voxel size (4.6 x 10{sup -3} cc) within an elliptical ROI that included the tumor area. Only voxels with a threshold {ge} 2 in relation to the average scalp Tl-201 uptake were included and this total number of voxels expressed in cc was compared to previously established maximal tumor/scalp Tl-201 uptake ratios (T/S) and histopathology. Results are presented as the median (min-max) and differences were considered significant for p
    Journal of Nuclear Medicine. 04/1995; 36(Suppl.5).
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    ABSTRACT: Cocaine abuse continues to be a major public health concern, with a variety of medical and neurologic sequelae. Previous studies have demonstrated abnormalities in cerebral perfusion in chronic cocaine abusers and after acute administration of cocaine. Although women are becoming increasingly represented among drug abusers, few studies have included women. To the authors' knowledge, none has compared cerebral perfusion in asymptomatic women with that in men. The cerebral perfusion of 13 cocaine-dependent women, 4 of whom were also heroin dependent, was studied with 99mTc hexamethylpropyleneamine oxime (HMPAO) SPECT. These women were compared with 13 cocaine-dependent men and 26 healthy control subjects. Structural brain lesions and neurologic abnormalities were excluded by MRI and neurologic evaluation. Perfusion studies were interpreted in a standardized fashion by reviewers blinded to clinical information. It was found that cocaine-dependent women were much less likely to have abnormal study findings than cocaine-dependent men (p = 0.003) and were indistinguishable from normal women (p = 1.0). However, the results in both women and men who concurrently used heroin plus cocaine were all abnormal. Perfusion abnormalities tended to be located in anterior brain structures, such as the frontal and temporal cortex and the basal ganglia. These data suggest that cocaine-dependent women have fewer abnormalities in cerebral perfusion than cocaine-dependent men, but that concurrent abuse of heroin and cocaine is associated with more perfusion abnormalities in both sexes.
    Journal of Nuclear Medicine 01/1995; 35(12):1902-9. · 5.77 Impact Factor
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    ABSTRACT: Artificial neural networks have been applied to a variety of pattern recognition tasks in medical imaging and have been shown to be a powerful classification tool. The potential usefulness to discriminate normal from abnormal cerebral perfusion patterns was investigated. Cerebral perfusion imaging with 99mTc-labeled hexamethylpropyleneimine oxime was performed on 52 normal control subjects, 29 patients with clinically diagnosed Alzheimer's disease (AD) and 25 patients with chronic cocaine polydrug abuse. Each study was registered and scaled to a common anatomic coordinate system, yielding 120 standardized cortical regions. A back-propagation neural network classifier based on regional perfusion was used to classify normal and abnormal perfusion patterns. The neural network was trained to discriminate patients with AD from age-matched normal controls and cocaine polydrug abuse patients from normal controls. The performance of the neural network in these two tasks was evaluated quantitatively by receiver operating characteristic (ROC) analysis using cross-validation. For patients with AD, the area under the ROC curve was 0.93 +/- 0.04. When testing with the cocaine polydrug abuser data, the area under the ROC curve was 0.89 +/- 0.04. Neural networks provide a potentially useful tool in the decision-making task to discriminate patients with AD and cocaine abuse from normal controls.
    Journal of Nuclear Medicine 06/1994; 35(5):771-4. · 5.77 Impact Factor
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    ABSTRACT: Chronic fatigue syndrome is an illness of unknown origin that begins abruptly with a flulike state and has symptoms suggesting both a chronic viral encephalitis and an affective disorder. We compared single-photon emission computed tomography (SPECT) scans of patients with chronic fatigue syndrome with those of patients with AIDS dementia complex and unipolar depression. We used 99mTc-hexamethylpropyleneamine oxime to examine 45 patients with chronic fatigue syndrome, 27 patients with AIDS dementia complex, and 14 patients with major unipolar depression. Scans of 38 healthy persons were used as controls. Comparison of regional defects between groups, as well as midcerebral uptake indexes (an objective measure of global radionuclide uptake), was performed by using analysis of variance with the Student-Newman-Keuls option. Correlation between the number of regional defects and the midcerebral uptake index was determined by using the Spearman rank-correlation test. Patients with AIDS dementia complex had the largest number of defects (9.15 per patient) and healthy patients had the fewest defects (1.66 per patient). Patients with chronic fatigue syndrome and depression had similar numbers of defects per patient (6.53 and 6.43, respectively). In all groups, defects were located predominantly in the frontal and temporal lobes. The midcerebral uptake index was found to be significantly lower (p < .002) in the patients with chronic fatigue syndrome (.667) and patients with AIDS dementia complex (.650) than in patients with major depression (.731) or healthy control subjects (.716). Also, a significant negative correlation was found between the number of defects and midcerebral uptake index in patients with chronic fatigue syndrome and AIDS dementia complex, but not in depressed patients or control subjects. These findings are consistent with the hypothesis that chronic fatigue syndrome may be due to a chronic viral encephalitis; clinical similarities between chronic fatigue syndrome and depression may be due to a similar distribution and number of defects in the two disorders.
    American Journal of Roentgenology 04/1994; 162(4):943-51. · 2.90 Impact Factor
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    ABSTRACT: Chronic fatigue syndrome is a recently characterized condition of unknown origin that is manifested by fatigue, flulike complaints, and neurologic signs and symptoms, including persistent headache, impaired cognitive abilities, mood disorders, and sensorimotor disturbances. This syndrome can be difficult to diagnose clinically or by standard neuroradiologic tests. We performed MR imaging and single-photon emission computed tomography (SPECT) in patients with chronic fatigue syndrome to compare the usefulness of functional and anatomic imaging in the detection of intracranial abnormalities. Sixteen patients who fulfilled the Centers for Disease Control, British, and/or Australian criteria for chronic fatigue syndrome had MR and SPECT examinations within a 10-week period. Axial MR and SPECT scans were analyzed as to the number and location of focal abnormalities by using analysis of variance with the Student-Newman-Keuls option. MR imaging findings in patients with chronic fatigue syndrome were compared with those in 15 age-matched control subjects, and SPECT findings in the patients with chronic fatigue syndrome were compared with those in 14 age-matched control subjects by using Fisher's exact test. The findings on MR and SPECT scans in the same patients were compared by using the Wilcoxon matched-pairs signed-ranks test. MR abnormalities consisted of foci of T2-bright signal in the periventricular and subcortical white matter and in the centrum semiovale; there were 2.06 foci per patient, vs 0.80 foci per control subject. MR abnormalities were present in eight (50%) of 16 patients, compared with three (20%) of 15 age-matched control subjects. Neither of these differences reached significance, although the power of the study to detect differences between groups was small. Patients with chronic fatigue syndrome had significantly more defects throughout the cerebral cortex on SPECT scans than did normal subjects (7.31 vs 0.43 defects per subject, p < .001). SPECT abnormalities were present in 13 (81%) of 16 patients, vs three (21%) of 14 control subjects (p < .01). SPECT scans showed significantly more abnormalities than did MR scans in patients with chronic fatigue syndrome (p < .025). In the few patients who had repeat SPECT and MR studies, the number of SPECT abnormalities appeared to correlate with clinical status, whereas MR changes were irreversible. SPECT abnormalities occur more frequently and in greater numbers than MR abnormalities do in patients with chronic fatigue syndrome. SPECT may prove to be useful in following the clinical progress of patients with this syndrome.
    American Journal of Roentgenology 04/1994; 162(4):935-41. · 2.90 Impact Factor
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    ABSTRACT: Tc-99m hexamethylpropylene amineoxime (HMPAO) brain perfusion SPECT was correlated with CT, MRI, and clinical findings in 17 patients with acute and subacute aphasia to determine its diagnostic potential in the early phases of stroke-associated language dysfunction. SPECT was performed using a dedicated brain imaging system after intravenous injection of 20 mCi (740 MBq) of Tc-99m HMPAO. Transaxial and three-dimensional surface rendered images were evaluated visually, and perfusion defects were correlated with CT, MRI, and a standard battery of clinical tests for aphasia. Clinical examination was insufficient for anatomic localization of aphasia in more than 40% of patients. CT exams were normal in 5 patients, although SPECT demonstrated perfusion defects in all 17. Nonfluent aphasia was present in only 6 of 10 patients with perfusion defects in Broca's area and fluent aphasia was present in only 5 of 10 patients with lesions in Wernicke's area. Auditory comprehension defect was associated with perfusion defects in the inferior parietal region in 9 of 12 patients (P = 0.05); reading and writing abnormalities were associated with perfusion defects in the posterior frontal, superior and inferior parietal cortex, and superior temporal gyri, and repetition deficit was associated with defects involving the inferior parietal cortex, the supramarginal and angular gyri, and the ipsilateral thalamus in 8 of 11 patients (P < 0.05). Brain perfusion SPECT should be included in the initial evaluation of aphasic patients, because clinical tests of aphasia and morphological imaging have limited value for accurately determining the extent and location of functional deficits.
    Clinical Nuclear Medicine 12/1993; 18(12):1032-8. · 2.96 Impact Factor
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    ABSTRACT: To improve the diagnostic utility of brain single-photon emission computed tomography (SPECT) in Alzheimer's disease (AD), we have developed and evaluated an objective method of differentiating patients and healthy elderly controls using a quantitative image analysis protocol. HMPAO-SPECT image datasets from 29 patients with probable AD and 78 age-matched controls were registered to a common anatomic frame of reference. Activity levels within 120 standardized cortical volumes were determined by an automated procedure. Subjects were classified into normal and AD groups by quadratic discriminant analysis using two features: global average activity level and average normalized activity levels within the two clusters of standardized volumes identified as most significantly different in AD by analysis of covariance. The classification used split-half replication to ensure valid results. Classification performance quantified by the area under a binormal ROC curve fitted to the data was 0.923 +/- 0.036; at a threshold likelihood ratio of 1, the sample sensitivity was 91% and specificity was 86%. We conclude that quantitative SPECT accurately distinguishes AD patients from elderly controls.
    Journal of Nuclear Medicine 12/1993; 34(11):2044-8. · 5.77 Impact Factor

Publication Stats

741 Citations
91.54 Total Impact Points

Institutions

  • 1992–1997
    • Boston Children's Hospital
      • Department of Radiology
      Boston, MA, United States
  • 1992–1994
    • Brigham and Women's Hospital
      • Department of Radiology
      Boston, MA, United States
  • 1993
    • Dana-Farber Cancer Institute
      Boston, Massachusetts, United States