Recent Publications

Study Reveals Association between Aβ, Tau, Circuitry and Cognition


A new study published in Nature Neuroscience revealed an association between Aβ, Tau, Circuitry and Cognition. The study was conducted by Dr. Heidi Jacobs, instructor at MGH Gordon Center and a Marie Curie Fellow, and Dr. Keith Johnson, leader of the Aging NeuroImaging Program at the MGH Gordon Center, and the Harvard Aging Brain Study.

Using longitudinal multimodal imaging data collected in healthy older individuals, they provided in vivo evidence in humans that amyloid deposition facilitates tau spread along structurally connected pathways and this combination of events is associated with memory decline.

Imaging modalities included positron-emission tomography (PET) and magnetic resonance imaging (MRI). PET imaging was performed using the tracer flortaucipir (FTP), which binds to tau pathology, and the tracer Pittsburg compound-B (PiB), which indicates amyloid deposition. MR imaging was performed using T1-weighted images to measure hippocampal volume, and diffusion tensor imaging (DTI) was used to measure tract diffusivity.

The results of this study showed that hippocampal volume at baseline, a proxy for neurodegenerative processes including tau pathology, predict changes in diffusivity in a tract innervating the hippocampus, the hippocampal cingulum bundle (HCB), and not in a control tract, the uncinate fasciculus (UF).

These diffusivity changes in the hippocampal cingulum bundle were in turn associated with accumulation of tau pathology outside the medial temporal lobe, in the connected posterior cingulate cortex (PCC), in individuals with elevated levels of amyloid pathology. Finally, the combination of these diffusivity changes in the hippocampal cingulum bundle and higher levels of posterior cingulate cortex tau were associated with memory decline in individuals with elevated levels of amyloid pathology. These findings suggests that amyloid plays a crucial role in driving neurodegenerative processes and cognitive decline, and that monitoring spread of tau pathology will be important in clinical trials focused on removing amyloid plaques in the earliest stages of the diseases.

A detailed summary of this study is featured in AlzForum.

Associations between tract diffusivity, tau accumulation in the PCC, amyloid pathology and memory performance

Jacobs HI, Hedden T, Schultz AP, Sepulcre J, Perea RD, Amariglio RE, Papp KV, Rentz DM, Sperling RA, Johnson KA. "Structural tract alterations predict downstream tau accumulation in amyloid-positive older individuals" Nat Neurosci. 2018 Feb 5;

Improving PET Quantitation with Denoising, Motion Compensation, and Deblurring


This article was published in the Nuclear & Plasma Sciences Society newsletter of September 2017

Positron emission tomography (PET) enables 3D visualization of vital physiological information, e.g., metabolism, blood flow, and neuroreceptor concentration by using targeted radioisotope-labeled tracers. Quantitative interpretation of PET images is crucial both in diagnostic and therapeutic contexts. As a result of its unique functional capabilities, PET imaging plays a pivotal role in diagnostics and in therapeutic assessment in many areas of medicine, including oncology, neurology, and cardiology. Accurate quantitation requires correction of PET raw data and/or images for a number of physical effects. These include attenuation correction, randoms and scatter correction, subject motion correction, and partial volume correction. We have developed a range of techniques that address the PET denoising, motion compensation, deblurring problems. Several of these methods greatly enhance the quantitative capabilities of PET particularly by incorporating information from an anatomical imaging modality such as magnetic resonance imaging (MRI).

Faced with a fundamental tradeoff between radiation dose and image noise, PET data is inherently noisy. The high levels of noise in PET images pose a challenge to accurate quantitation. This issue is particularly well pronounced at the early time frames of dynamic PET images, which are usually short to capture rapid changes in tracer uptake patterns. In order to improve image quality and quantitative accuracy, statistical image reconstruction algorithms model the Poisson characteristics of PET data and employ numerical optimization algorithms to solve the corresponding optimization problem [1, 2]. Common reconstruction procedures, such as ordered subsets expectation maximization, are therefore routinely followed by a post-filtering step for denoising the reconstructed image. A range of strategies have been proposed for post-reconstruction denoising of both static and dynamic PET images [3, 4]. In recent years, image denoising based on non-local means (NLM) has become popular [5]. Unlike conventional neighborhood filters, which use local similarities, in this technique, the search for voxels similar to a given voxel is no longer restricted to its immediate vicinity.

Full article in PDF

Heat-induced-radiolabeling and click chemistry


Yuan H, Wilks MQ, El Fakhri G, Normandin MD, Kaittanis C, Josephson L (2017) Heat-induced-radiolabeling and click chemistry: A powerful combination for generating multifunctional nanomaterials. PLoS ONE 12(2): e0172722. doi:10.1371/journal.pone.0172722


A key advantage of nanomaterials for biomedical applications is their ability to feature multiple small reporter groups (multimodality), or combinations of reporter groups and therapeutic agents (multifunctionality), while being targeted to cell surface receptors. Here a facile combination of techniques for the syntheses of multimodal, targeted nanoparticles (NPs) is presented, whereby heat-induced-radiolabeling (HIR) labels NPs with radiometals and socalled click chemistry is used to attach bioactive groups to the NP surface. Click-reactive alkyne or azide groups were first attached to the nonradioactive clinical Feraheme (FH) NPs. Resulting ªAlkyne-FHº and ªAzide-FHº intermediates, like the parent NP, tolerated 89Zr labeling by the HIR method previously described. Subsequently, biomolecules were quickly conjugated to the radioactive NPs by either copper-catalyzed or copper-free click reactions with high efficiency. Synthesis of the Alkyne-FH or Azide-FH intermediates, followed by HIR and then by click reactions for biomolecule attachment, provides a simple and potentially general path for the synthesis of multimodal, multifunctional, and targeted NPs for biomedical applications. Download Full Article in PDF

Outline of heat induced radiolabeling (HIR) and click chemistry surface functionalization used to obtain multimodal, targeted NPs.

Neuroplastic Changes in Blind Individuals



This article was initially published by the RSNA Daily Bulletin on November 30, 2016.

Dr. Laura Ortiz-Terán is a clinical radiologist and neuroimaging research scientist at the MGH Gordon Center. She works with Dr. Jorge Sepulcre to investigate the neuroplastic changes occurring in blind individuals, adults and children, using graph theory based resting-state functional connectivity analysis.

Medical Physics Cover Article



In the featured article of the latest volume of Medical Physics, researchers of the Gordon Center have presented a complete data acquisition and processing framework for respiratory motion compensated image reconstruction (MCIR) using simultaneous whole body PET/magnetic resonance (MR) and validated it through simulation and clinical patient studies.

By developing and validating a PET/MR pulmonary imaging framework, the authors show that simultaneous PET/MR, unique in its capability of combining structural information from MR with functional information from PET, shows promise in pulmonary imaging.

Joyita Dutta, Chuan Huang, Quanzheng Li and Georges El Fakhri. Pulmonary imaging using respiratory motion compensated simultaneous PET/MR. Med Phys 42, 4227 (2015);

[Link to article]

New Book



A book Statistical Computing in Nuclear Imaging authored by a member of the center Dr. Arkadiusz Sitek was recently published by the CRC Press.

Statistical Computing in Nuclear Imaging introduces aspects of Bayesian computing in nuclear imaging. The book provides an introduction to Bayesian statistics and concepts and is highly focused on the computational aspects of Bayesian data analysis of photon-limited data acquired in tomographic measurements.

Read more

Recent Publications


Recent publications are listed below.

For a full list of publications, please see the Publications page.

  • W. Zhu, Q. Li, B Bai, PS Conti, RM Leahy. Patlak image estimation from dual time-point list-mode PET data. IEEE Trans. Medical Imaging, in press, 2014
  • Y. Petibon, C. Huang, J. Ouyang, T. G Reese, Q. Li, S. Syrkina, Y-L Chen and G. El Fakhri. Relative role of motion and PSF compensation in whole-body oncologic PET-MR imaging. Medical Physics, in press, 2014
  • Bai B, Lin Y, Zhu W, Ren R, Li Q, Dahlbom M, Difilippo F, Leahy RM. MAP reconstruction for Fourier rebinned TOF-PET data. Phys Med Biol. 2014 Feb 21; 59(4):925-49.
    View in: PubMed
  • Y. Lin, J. P. Haldar, Q. Li and R. M. Leahy. Sparse Constrained Mixture Modeling for the Estimation of Kinetic Parameters in Dynamic PET. IEEE Transactions on Medical Imaging. 2014; 33(1):173-185.
  • Guo J, Guo N, Lang L, Kiesewetter DO, Xie Q, Li Q, Eden HS, Niu G, Chen X. 18F-Alfatide II and 18F-FDG Dual-Tracer Dynamic PET for Parametric, Early Prediction of Tumor Response to Therapy. J Nucl Med. 2014 Jan; 55(1):154-60.
    View in: PubMed

Nature Publication


Publication in Nature
Charalambos Kaittanis, Travis M. Shaffer, Anuja Ogirala, Santimukul Santra, J. Manuel Perez, Gabriela Chiosis, Yueming Li, Lee Josephson & Jan Grimm. Environment-responsive nanopores for therapy and treatment monitoring via molecular MRI quenching.
Nature Commun. 5, March 2014

[PubMed link] [Nature link]

Reprinted by permission from Macmillan Publishers Ltd: Nature Communications, copyright 2014