S C Huang

University of California, Los Angeles, Los Angeles, California, United States

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Publications (237)960.26 Total impact

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    ABSTRACT: Whether perceived changes in memory parallel changes in brain pathology is uncertain. Positron emission tomography (PET) scans using 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP) can measure levels of amyloid plaques and tau neurofibrillary tangles in vivo. Here we investigate whether degree of self-reported memory impairment is associated with FDDNP-PET binding levels in persons without dementia. Fifty-seven middle-aged and older adults without dementia (mean age ±standard deviation = 66.3 ± 10.6 years), including 25 with normal aging and 32 with mild cognitive impairment (MCI), were assessed. The outcome measures were the four factor scores of the Memory Functioning Questionnaire (MFQ) (frequency of forgetting, seriousness of forgetting, retrospective functioning, and mnemonics use) and FDDNP-PET binding levels in medial temporal, lateral temporal, posterior cingulate, parietal, frontal, and global (overall average) regions of interest. After controlling for age, higher reported frequency of forgetting was associated with greater medial temporal (r = -0.29, p = 0.05), parietal (r = -0.30, p = 0.03), frontal (r = -0.35, p = 0.01), and global FDDNP-PET binding levels (r = -0.33, p = 0.02). The remaining MFQ factor scores were not significantly associated with FDDNP-PET binding levels, and no significant differences were found between normal aging and MCI subjects. Item analysis of the frequency of forgetting factor revealed five questions that yielded similar results as the full 32-question scale (r = -0.52, p = 0.0002). These findings suggest that some forms of memory self-awareness, in particular the reported frequency of forgetting, may reflect the extent of cerebral amyloid and tau brain pathology.
    International Psychogeriatrics 02/2012; 24(7):1076-84. · 2.19 Impact Factor
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    ABSTRACT: To determine the neuropathological load in the living brain of nondemented adults with Down syndrome using positron emission tomography with 2-(1-{6-[(2-fluorine 18-labeled fluoroethyl)methylamino]-2-napthyl}ethylidene) malononitrile ([(18)F]FDDNP) and to assess the influence of age and cognitive and behavioral functioning. For reference, [(18)F]FDDNP binding values and patterns were compared with those from patients with Alzheimer disease and cognitively intact control participants. Cross-sectional clinical study. Volunteer sample of 19 persons with Down syndrome without dementia (mean age, 36.7 years), 10 patients with Alzheimer disease (mean age, 66.5 years), and 10 controls (mean age, 43.8 years). Binding of [(18)F]FDDNP in brain regions of interest, including the parietal, medial temporal, lateral temporal, and frontal lobes and posterior cingulate gyrus, and the average of all regions (global binding). The [(18)F]FDDNP binding values were higher in all brain regions in the Down syndrome group than in controls. Compared with the Alzheimer disease group, the Down syndrome group had higher [(18)F]FDDNP binding values in the parietal and frontal regions, whereas binding levels in other regions were comparable. Within the Down syndrome group, age correlated with [(18)F]FDDNP binding values in all regions except the posterior cingulate, and several measures of behavioral dysfunction showed positive correlations with global, frontal, parietal, and posterior cingulate [(18)F]FDDNP binding. Consistent with neuropathological findings from postmortem studies, [(18)F]FDDNP positron emission tomography shows high binding levels in Down syndrome comparable to Alzheimer disease and greater levels than in members of a control group. The positive associations between [(18)F]FDDNP binding levels and age as well as behavioral dysfunction in Down syndrome are consistent with the age-related progression of Alzheimer-type neuropathological findings in this population.
    Archives of neurology 06/2011; 68(6):768-74. · 7.58 Impact Factor
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    ABSTRACT: In the field of quantitative imaging, the creation of accurate volumes of interest (VOIs) is often of central importance. However, the process of creating these VOIS for multiple subjects can be time-intensive and there are many chances to introduce variability on inter- and intra-investigator levels. Although previous work has shown that image normalization through cortical surface mapping can be helpful in VOI analysis, the process is complicated and labor-intensive. In this paper we present a method to eliminate this variability by warping structural and functional images to a common space in which valid VOIs already exist. We apply this method to a study of Alzheimer's disease (AD) and 2-(1-{6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP), which is known to co-localize with amyloid plaques and neurofibrillary tangles. We normalize the MRIs of control subjects and mild cognitive impairment (MCI) and AD patients, to a common space. The same normalization is applied to FDDNP PET images. The normalization technique reduces average voxel-to-voxel variance in MRIs by 54% as compared to linear normalization alone. Biologically important structures, such as the segmentation between white and gray matter, are maintained after normalization. Discriminant analysis shows that data extracted from VOIs in the common space out-performs data extracted from unnormalized PET images in classifying subjects as control, MCI, or AD. This suggests that image normalization may be useful in eliminating inter- and intra-investigator variability and increasing the predictive capability of data extracted from imaging modalities. Further study will examine the applicability of this method to predicting longitudinal changes in cognitive ability from functional imaging data.
    Nuclear Science Symposium Conference Record (NSS/MIC), 2010 IEEE; 01/2010
  • Alzheimers & Dementia - ALZHEIMERS DEMENT. 01/2010; 6(4).
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    ABSTRACT: Amyloid senile plaques and tau neurofibrillary tangles are neuropathological hallmarks of Alzheimer disease that accumulate in the brains of people without dementia years before they develop dementia. Positron emission tomography (PET) scans after intravenous injections of 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP), which binds to plaques and tangles in vitro, demonstrate increased cerebral binding in patients with Alzheimer disease compared with cognitively intact controls. Here we investigated whether known risk factors for Alzheimer disease and dementia are associated with FDDNP-PET binding. To determine if impaired cognitive status, older age, apolipoprotein E-4 (APOE-4) genetic risk for Alzheimer disease, family history of dementia, and less education are associated with increased regional cerebral FDDNP-PET binding. Cross-sectional clinical study. A university research institute. Volunteer sample of 76 middle-aged and older persons without dementia (mean age, 67 years) including 36 with mild cognitive impairment. Of the 72 subjects with genetic data, 34 were APOE-4 carriers. The FDDNP-PET signal in brain regions of interest, including medial and lateral temporal, posterior cingulate, parietal, and frontal. For all regions studied, cognitive status was associated with increased FDDNP binding (P < .02 to .005). Older age was associated with increased lateral temporal FDDNP binding. Carriers of APOE-4 demonstrated higher frontal FDDNP binding than noncarriers. In the mild cognitive impairment group, age was associated with increased medial and lateral temporal FDDNP binding, and APOE-4 carriers had higher medial temporal binding than noncarriers. Impaired cognitive status, older age, and APOE-4 carrier status are associated with increased brain FDDNP-PET binding in persons without dementia, consistent with previous clinical and postmortem studies associating these risk factors with amyloid plaque and tau tangle accumulation. Stratifying subject groups according to APOE-4 carrier status, age, and cognitive status may therefore be an informative strategy in future clinical trials using FDDNP-PET.
    Archives of general psychiatry 01/2009; 66(1):81-7. · 12.26 Impact Factor
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    ABSTRACT: Information on the transport and phosphorylation rate constants (k1,k2,k3,k4,Ki) of a tracer reflects the biological state of cells. A microfluidic cell culture chip coupled with PSAPD camera (MF-PSAPD) has been developed to give continuous measurements of radioactivity in individual wells. However, constant infusion (CI) of PET tracers through the chambers would give high background activity due to the relatively large volume space of the infusing medium in the wells of cultured cells that compromise the ability of the setup to estimate the k values. New strategies of controlling the infusion and tracer level are needed to provide reliable estimates of the parameters. A switching strategy (SS) was conceived that consists of multiple medium-infusion cycles, each of which has a tracer incubation (TI) period followed by a background-removed (BR) period (tracer-free medium). In this paper, equally switching strategy (ESS) with 12 cycles of constant TI and BR periods (5 min each) was evaluated by computer simulation and by experiments on MF-PSAPD using the tracer fluorodeoxy-glucose (FDG) and the four parameter FDG model. The SS was further optimized by using a simulated annealing algorithm and D-optimal criterion to obtain optimal switching strategy (OSS). Simulations showed that the 12-cycle ESS did not perform as well (i.e., with larger estimated variability of the model parameters) as a 5-cycle OSS that also has multiple practical advantages. Patterns of OSS were found to be insensitive to the variation of cell number and k values, and all tended to have longer TI at the beginning but longer BR at later times. Estimated k values with SS have large reduction in %CV compared to those of CI, with the largest reduction for Ki--from 762% down to 26% under the same count rate conditions. The new optimized strategy of tracer incubation/measurement is able to provide reliable estimates of FDG k's in MF-PSAPD.
    IEEE Nuclear Science Symposium conference record. Nuclear Science Symposium 01/2009;
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    ABSTRACT: 3'-[F-18]fluoro-3'-deoxythymidine (FLT) traces thymidine phosphorylation catalyzed by thymidine kinase during cell proliferation. Knowing the rate of cell proliferation during cancer treatment, such as radiation therapy, would be valuable in assessing whether tumor recurrence is likely and might indicate the need for additional treatments. However, the relationship between FLT kinetics and the effects of radiation is not well-understood. Nor has the method for optimal quantification of FLT uptake within the irradiated tumor microenvironment been extensively examined. We performed dynamic FLT-positron emission tomography (PET) studies (60 min) on 22 mice implanted subcutaneously with syngeneic mammary MCaK tumors bilaterally in the shoulder area. A day before the FLT-PET imaging, the tumor on the right side was irradiated with a single dose (0, 2.5, 5, 10, or 20 Gy) or with fractionated exposures (4x2.5 Gy given in 12 h intervals). Standardized uptake value (SUVs) of FLT on tumors at 10 and 60 min post injection were calculated; model fitting was used to estimate the kinetic parameters. Significant radiation-induced changes were shown by comparing the irradiated tumor with the control tumor in the same animal and by comparing it to nonirradiated mice. The effect of radiation on MCaK cell cycle parameters and FLT uptake was also examined in vitro. In vivo FLT kinetics were sensitive to radiation doses of 5 Gy and higher (administered 1 day earlier), as judged by SUV semiquantitative measures and by modeling. Single irradiation with 10 Gy had greater impact on SUVs and kinetic parameters than fractionated exposures. Overall, the uptake constant Ki appeared to be the best marker for these radiation effects. FLT uptake by irradiated cells in vitro at various doses gave similar findings, and the in vitro FLT uptake correlated well with Ki. Radiation-induced G2/M arrest appeared to influence FLT uptake, and this was more pronounced after single than fractionated doses. The kinetics of FLT uptake into murine mammary tumors was altered 1 day after radiation treatment. The dose-dependent response correlated well with in vitro FLT cellular uptake. Parameters (e.g., Ki) derived from FLT kinetics are expected to be useful for assessing the efficacy of irradiation treatment of tumors.
    Molecular Imaging & Biology 09/2008; 10(6):325-34. · 3.10 Impact Factor
  • Alzheimer's and Dementia 07/2008; 4(4). · 17.47 Impact Factor
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    ABSTRACT: Establish new approaches for early diagnosis of dementia, based on imaging amyloid and tau pathology, cell losses and neuronal function, in subjects with mild cognitive impairment (MCI),. The overall aim is to develop effective tools for monitoring disease progression in the living patient to facilitate discovery of early therapeutic interventions to modify the course of the disease. Use 2-(1-{6-[(2-[F- 18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([F-18]FDDNP) in combination with positron emission tomography (PET) to produce dynamic images for quantification of regional cortical brain deposition in MCI patients and compare them with controls subjects and patients with Alzheimer's disease (AD). Comparison with other molecular imaging probes for neuronal losses and function were also made. Patients are positioned supine in the tomograph bed with his/her head in the detector ring field. Upon injection of the molecular imaging probe (e.g., [F-18]FDDNP) images are obtained at very short time intervals for up to two hours. This results in dynamic sequences of brain distribution of the probe. Patients with clinical diagnosis of AD, MCI and control subjects. Subjects in the categories established above were scanned with [F-18]FDDNP-PET and quantification performed using Logan parametric graphical analysis to measure relative quantitative amyloid loads throughout the brain within patient groups. These results were compared in the same patients with cell losses in hippocampus using 4-[F-18]fluoro-N-{2-[4-(2-methoxyphenyl)- 1-piperazinyl]ethyl}-N-(2-pyridinyl)benzamide,([F-18]MPPF) and regional cerebral glucose metabolic rates using 2-deoxy-2-[F-18]fluoro-2-deoxy-D-glucose (2-[F-18]FDG). [F-18]FDDNP reliably follows neuropathological progression (amyloid plaques [SP]; neurofibrillary tangles [NFT]) in the living brain of AD patients and those with MCI. The distribution of [F-18]FDDNP brain cortical accumulation correlates well with behavioral measures (e.g., MMSE scores) and follows known patterns of pathological distribution observed at autopsy. We have also established conversion of controls to MCI and MCI to AD with precision and sensitivity in patients and control subjects in follow-up studies. Moreover, we have established that hemispheric cortical surface mapping of [F-18]FDDNP binding is a powerful tool for assessment and visualization of the rate of brain pathology deposition. A strong correlation of [F-18]FDDNP binding, cell losses in hippocampus and decreased glucose utilization ([F-18]FDG PET) in several neocortical regions was found in the same AD and MCI subjects. The combined evaluation of [F-18]FDDNP PET (targeting NFT and_SP) with neuronal losses in the hippocampus and with [F-18]FDG PET (targeting neuronal function) offers the opportunity for reliable, noninvasive detection of MCI patients at risk for AD. The approach offers a glimpse to the molecular and cellular mechanisms associated with dementia and provides a means for their assessment in the living patient. Monitoring disease progression in MCI patients demonstrates the usefulness of this imaging approach for early diagnosis and provides a means for evaluation of neuroprotective agents and drugs aimed at prevention and modification of disease progression.
    The Journal of Nutrition Health and Aging 02/2008; 12(1):61S-5S. · 2.39 Impact Factor
  • Alzheimers & Dementia - ALZHEIMERS DEMENT. 01/2008; 4(4).
  • Alzheimers & Dementia - ALZHEIMERS DEMENT. 01/2008; 4(4).
  • Alzheimers & Dementia - ALZHEIMERS DEMENT. 01/2008; 4(4).
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    ABSTRACT: A set of over 20 dynamic mouse FDG microPET images has been collected experimentally at UCLA and is made available to the public on the Internet. Accompanying each dynamic image set also is the radioactivity measurements of multiple sequential blood samples taken during the study. The data are expected to be useful for investigators who want to know more about the characteristics of dynamic mouse FDG microPET images before doing their own experiments, and will be especially useful for those who are interested in developing image-based methods for deriving blood activity curves from dynamic mouse microPET images.
    Nuclear Science Symposium Conference Record, 2006. IEEE; 12/2006
  • Article: IC103-02
    Alzheimers & Dementia - ALZHEIMERS DEMENT. 01/2006; 2(3).
  • Article: O3-06-06
    Alzheimers & Dementia - ALZHEIMERS DEMENT. 01/2006; 2(3).
  • Article: P2-274
    Alzheimers & Dementia - ALZHEIMERS DEMENT. 01/2006; 2(3).
  • Journal of Cerebral Blood Flow & Metabolism 07/2005; · 5.40 Impact Factor
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    ABSTRACT: This paper presents a novel approach to feature-based brain image warping, by using a hybrid implicit/explicit framework, which unifies many prior approaches in a common framework. In the first step, we develop links between image warping and the level-set method, and we formulate the fundamental mathematics required for this hybrid implicit/explicit approach. In the second step, we incorporate the large-deformation models into these formulations, leading to a complete and elegant treatment of anatomical structure matching. In this latest approach, exact matching of anatomy is achieved by comparing the target to the warped source structure under the forward mapping and the source to the warped target structure under the backward mapping. Because anatomy is represented nonparametrically, a path is constructed linking the source to the target structure without prior knowledge of their point correspondence. The final point correspondence is constructed based on the linking path with the minimal energy. Intensity-similarity measures can be naturally incorporated in the same framework as landmark constraints by combining them in the gradient descent body forces. We illustrate the approach with two applications: (1) tensor-based morphometry of the corpus callosum in autistic children; and (2) matching cortical surfaces to measure the profile of cortical anatomic variation. In summary, the new mathematical techniques introduced here contribute fundamentally to the mapping of brain structure and its variation and provide a framework that unites feature and intensity-based image registration techniques.
    NeuroImage 03/2005; 24(3):910-27. · 6.25 Impact Factor
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    ABSTRACT: Despite recent developments in high resolution small animal PET, cardiac studies in mice are still of limited quality due to the small size of the imaged organ and motion within the cardiac and respiratory cycle. By gating for one or both motions an improvement of the quantitative PET-data and images can be expected. We used a data acquisition and analysis system with multiple analog channel recording capability, consisting of a general purpose transducer amplifier for respiration and an ECG amplifier. A small plastic pressure pad connected to a pressure transducer served as respiratory sensor. To avoid artifacts in CT and attenuation corrected PET we used carbon electrodes and lead wires for ECG. Two digital trigger units received analog signals from both amplifiers and generated negative trigger impulses. The signal was fed into our microPET<sup>®</sup> and integrated into the listmode mode file. For reconstruction microPET<sup>®</sup> Manager (Concorde Microsystems) was used. The nongated CT was used for attenuation correction and anatomical orientation. With the system described we were able to generate reliable trigger pulses for both cardiac and respiratory motions. By eliminating inspiratory motion and reducing the influence of systolic spillover better quantitative blood pool values were achieved. A significant visual improvement in image quality was observed in diastole. The reconstruction process was computationally intensive due to the large number of sinograms generated in the histogramming process.
    Nuclear Science Symposium Conference Record, 2004 IEEE; 11/2004
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    ABSTRACT: In this study, we developed a simple and robust semiautomatic method to measure the right ventricle to left ventricle (RV-to-LV) transit time (TT) in mice using 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). The accuracy of the new method was first evaluated using a 4-D digital dynamic mouse phantom. The RV-to-LV TTs of thirty-two mice studies were measured using the new method and compared to those obtained from the conventional ROI-drawing method. The results showed that the new method accurately separated different structures (e.g. RV, lung and LV) in the PET images and generated corresponding time activity curve (TAC) of each structure. The RV-to-LV TTs obtained from the new method and ROI method were not statistically different (p=0.31; r=0.77). We expect that this fast and robust method is applicable to study the pathophysiology of cardiovascular diseases using small animal models such as rats and mice.
    Nuclear Science Symposium Conference Record, 2004 IEEE; 11/2004

Publication Stats

9k Citations
960.26 Total Impact Points

Institutions

  • 1979–2012
    • University of California, Los Angeles
      • • Department of Molecular and Medical Pharmacology
      • • Department of Psychiatry and Biobehavioural Sciences
      • • Department of Neurology
      • • Department of Biomathematics
      • • Department of Medicine
      Los Angeles, California, United States
    • University of Southern California
      • • Department of Psychiatry and Behavioral Sciences
      • • Department of Biological Sciences
      Los Angeles, CA, United States
  • 1982–2005
    • Children's Hospital Los Angeles
      • • DIvision of Neurology
      • • Division of Psychiatry
      Los Angeles, California, United States
  • 1999
    • Sungkyunkwan University
      • Department of Nuclear Medicine
      Sŏul, Seoul, South Korea
  • 1993–1998
    • University of Sydney
      • Biomedical and Multimedia Information Technology Research Group (BMIT)
      Sydney, New South Wales, Australia
    • Institute of Biological Engineering
      Lexington, Kentucky, United States
  • 1995–1997
    • Chung Yuan Christian University
      臺中市, Taiwan, Taiwan
  • 1988
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States
  • 1986
    • CSU Mentor
      Long Beach, California, United States