Entries in PET (6)

Monday
Jul102017

Childhood epilepsy may be associated with increased β-amyloid accumulation in adulthood

Adults with childhood-onset epilepsy appear to have increased β-amyloid (Aβ) plaque accumulation compared to healthy controls, according to a recently published study conducted in Finland [1]. Brain Aβ plaque deposition was analyzed in 41 participants from a cohort of late middle- aged individuals with childhood-onset epilepsy and 46 matched controls using carbon 11-labeled Pittsburgh Compound B (PiB) positron emission tomography (PET) [1].  Aβ plaque accumulation, a well- known hallmark of Alzheimer’s disease (AD), occurs in the brain years before the appearance of the first cognitive symptoms [2]. The participants with childhood-onset epilepsy are involved in the Turku Adult Childhood Onset Epilepsy TACOE study [3], which has followed them for 5 decades.

Childhood epilepsy was associated with increased PiB uptake compared to controls [1]. In a semi-quantitative analysis, the AD risk gene, APO ε4, together with idiopathic epilepsy, was also found to be associated with increased PiB uptake [1]. The findings are noteworthy as the effects of childhood epilepsy on the brain and cognition later in life are not well understood. Future studies are needed to examine whether childhood epilepsy might be a risk factor for AD. Well known risk factors for AD include Down syndrome, genetic abnormalities, cardiovascular disease and traumatic brain injury [2, 4]. AD is the most common form of dementia and there is no treatment [2]. At present, an estimated 5.4 million Americans have Alzheimer's disease [2].

-JKR

 

 [1] Joutsa J, Rinne JO, Hermann B, Karrasch M, Anttinen A, Shinnar S, Sillanpää M. Association Between Childhood-Onset Epilepsy and Amyloid Burden 5 Decades Later. JAMA Neurol. 2017;74(5):583-590.

[2] Alzheimer's Association. 2016 Alzheimer's disease facts and figures. Alzheimers Dement. 2016;12(4):459-509.

[3] Sillanpää M, Jalava M, Kaleva O, Shinnar S. Long-term prognosis of seizures with onset in childhood. N Engl J Med. 1998;338(24):1715-22.

[4] Zigman WB, Lott IT. Alzheimer's disease in Down syndrome: neurobiology and risk. Ment Retard Dev Disabil Res Rev. 2007;13(3):237-46.

Wednesday
Oct212015

Isotopes Beyond PET

Being in a lab that uses short-lived radioactive isotopes to study the human brain, we sometimes forget the utility of long-lived isotopes in other scientific fields. Reading the recent report of Bell et al. that indicates a potential for life developing on Earth as early as 4.1 Billion years ago,1 I was reminded of the vast historical knowledge humans have gained through isotopic measurement. In this study, zircons from the Jack Hills in Australia, known for containing the oldest terrestrial-formed material on Earth,2 were uranium-lead dated (4.1 Ga) and analyzed for the presence of partially disordered graphite (i.e. carbon, the atom of life). Zircons with graphite were analyzed for the presence of > 40 nm cracks—thanks to synchrotron transmission X-ray microscopy—to avoid regions that may have gathered carbon-based material after zircon formation. Crack-less regions were analyzed for evidence of biogenic carbon through 12C/13C isotopic ratio measurement.3 The 12C/13C ratio found in carbon-based inclusions in the Jack Hills zircon was consistent with the known biogenic carbon signature, suggesting that life may have had its start as early as 4.1 billion years ago, 300 million years earlier than previous reports.4 If earlier development of planetary life is the norm, it would increase current estimates of the prevalence of life throughout the universe. Bring on the aliens!

~GV

1)      Bell, E. A. et al. (2015). "Potentially biogenic carbon preserved in a 4.1 billion-year-old zircon". PNAS, doi: 10.1073/pnas.1517557112.

2)      Wilde, S. A.; et al. (2001). "Evidence from detrital zircons for the existence of continental crust and oceans on the Earth 4.4 Gyr ago." Nature 409 (6817):175–178.

3)      Schopf JW, Kudryavtsev AB (2014) Biogenicity of Earth’s earliest fossils. Evolution of Archean Crust and Early Life, Modern Approaches in Solid Earth Sciences, eds Dilek Y, Furnes H (Springer, Dordrecht, The Netherlands), Vol 7, pp 333–349.

4)      Mojzsis SJ, et al. (1996) Evidence for life on Earth before 3,800 million years ago. Nature 384 (6604):55–59.

Tuesday
Aug182015

The earliest central nervous system identified in a 520-million-year-old fossil

The earliest known complete central nervous system was discovered in a well preserved Cambrian great appendage arthropod fossil. This creature belongs to a now extinct group of animals that had a pair of long, claw-like extensions attached to their heads. The fossil was found in Chengjiang, Yunnan Province, China, which is known for its exceptionally preserved early Cambrian (ca. 510~550 mya) marine fossils.


The team utilized different imaging techniques, including energy-dispersive X-ray fluorescence and X-ray computed tomography, to trace the iron deposits that had selectively accumulated in the nervous system during fossilization. The creature has one optic neuropil separate from a protocerebrum contiguous with four head ganglia, succeeded by eight contiguous ganglia in an eleven-segment trunk. This is similar to today’s Chelicerata, a group of arthropods that include spiders, scorpions and horseshoe crabs.

 

 

References:

(1) Tanaka, G.; Hou, X.; Ma, X.;Edgecombe, G.D.; Strausfeld, N.J. Nature, 2013, 502, 364-367.

(2) Chen, J.; Waloszek, D.; Maas, A. Lethaia, 2004, 37, 3-20.

Monday
Jun152015

Intraoperative PET Imaging: The Advanced Multimodality Image Guided Operating Suite (AMIGO)

Several weeks ago, at the World Medical Innovation Forum, doctors and scientists from Brigham and Women’s Hospital presented their 20 million dollar AMIGO imaging suite complete with an operating room, MRI room, mass spectrometry instrumentation, and a PET/CT room for image-guided neurosurgeries. The current foci for this high-tech operating suite – which all rely heavily on the MRI functionality – are: 1) correcting preoperative brain images during surgery for navigation, 2) monitoring temperature for brain tumor thermal ablations, and 3) identifying residual tumor tissue at the end of surgery.1 More recently, mass spectrometry has been used intraoperatively in the AMIGO suite to map brain tumor margins through detection of an onco-metabolite,  2-hydroxyglutarate, which is produced in relatively large quantities by gliomas with mutations in isocitrate dehydrogenases 1 and 2.2 Considering my current research focus is development of new radiotracers, I was especially intrigued by the addition of PET imaging to this operating suite, which appears to be included for applications in tumor mapping and validating tumor excision completeness during surgery.3 Beyond tumor imaging, there are many radiotracers that provide important molecular and functional information about the brain, particularly the occupancy of neuroreceptors. Is there a place for these radiotracers in intraoperative neuroimaging?

~GV

1)      Jolesz, FA. (2011) Intraoperative imaging in neurosurgery: where will the future take us? Acta Neurochir Suppl, 109, 21-25.

2)      Agar, YR et al. (2014) Intraoperative mass spectrometry mapping of an onco-metabolite to guide brain tumor surgery. PNAS, 111, 11121-11126.

3)      http://brighamandwomens.org/Research/amigo/inside_suite.aspx. Accessed 06/15/2015

Monday
Jun152015

The state of medical neuroscience: how can PET fill the gaps?

A couple of months ago I had an opportunity to attend the World Medical Innovation Forum hosted by Partners Health Care. This year’s forum focusing on Neuroscience brought together expertise from both industry and academia to discuss the current state of research for psychiatric and neurologic disease. This conference was rather unique in that it gave the audience a full spectrum view of how these diseases impact the world. While thoroughly covering the latest medical information on new pathological targets and therapeutic advances, the presenters also included patients and patients’ families, which offered a unique perspective that helped to characterize the disease as more than just a molecular mishap. While the science can often be slow and wrought with frustration, reconnection with patients and advocates for disease research can quickly reset the stage to remind you of the end goal.

The forum did not include any detailed data presentations, but offered an informal, conversational approach to discussing the current interests of both industry and academic researchers. With respect to Alzheimer’s disease, the general consensus seemed to be that the current spectrum of therapies targets the removal of dysfunctional proteins (Aβ, Tau), but this might not be enough once the tissue is damaged. Industry called to academic researchers in basic research to identify targets for early diagnosis so that the disease can be caught before there is permanent damage. They also highlighted the need for regenerative methods to help repair the damaged tissue once the diseased tissue is removed. In this same vein, regenerative medicine methods were proposed where dopamine neurons will be implanted in Parkinson’s disease patients to replace those lost to the disease. In regards to MS research, the search for curative, neuroprotective, and restorative therapy continues to stop, prevent and repair the insult of neuronal damage brought on by this disease.

From a neuroimaging perspective, many stages in this research offer a potential for advancement with PET imaging. In vivo imaging provides an opportune view into the living brain whereby early AD biomarkers could be tracked non-invasively and evaluated with disease progression. In regenerative medicine, molecular imaging provides a chance to visualize whether newly implanted neurons are expressing proper receptors and neurotransmitters are interacting accordingly. Finally, when regenerative therapies are ready, PET imaging can not only provide structural proof, but hopefully also confirm that this new structure is molecularly sound.