Global and local fMRI signals driven by neurons defined optogenetically by type and wiring

Ars Technica has a nice writeup about a paper in Nature which isolates the BOLD signal from a specific type of neuron:

With everything in place, the researchers confirmed that firing an impulse in excitatory neurons produced a signal that matched nicely with the ones observed during regular experiments. Putting the channelrhodopsin into inhibitory neurons produced a small BOLD signal in the area where the light triggered an impulse, but it was surrounded by a halo of depressed activity, consistent with the neurons’ inhibitory role.

But the BOLD signals weren’t limited to the area where the light triggered activity. With a slight delay, signals started showing up in other areas of the brain, with the precise locations changing based on where exactly the activity was triggered. The authors indicate that these additional signals provide an indication of the brain’s wiring—the nerves at the site of the initial activity were simply doing what they normally did, and communicating with other areas of the brain. With enough time, they suggest, their technique could be used to map functional connections throughout the brain.

It’s impressive work that really takes aim at the foundation of fMRI and signal origin rather than most of the empirical neurologic applications that we usually see in the literature. I’m sure there must have been some work at this years’ ISMRM that went in a similar direction…

Here’s the full paper in Nature. Abstract:

Global and local fMRI signals driven by neurons defined optogenetically by type and wiring

Despite a rapidly-growing scientific and clinical brain imaging literature based on functional magnetic resonance imaging (fMRI) using blood oxygenation level-dependent (BOLD)1 signals, it remains controversial whether BOLD signals in a particular region can be caused by activation of local excitatory neurons2. This difficult question is central to the interpretation and utility of BOLD, with major significance for fMRI studies in basic research and clinical applications3. Using a novel integrated technology unifying optogenetic4, 5, 6, 7, 8, 9, 10, 11, 12, 13 control of inputs with high-field fMRI signal readouts, we show here that specific stimulation of local CaMKII?-expressing excitatory neurons, either in the neocortex or thalamus, elicits positive BOLD signals at the stimulus location with classical kinetics. We also show that optogenetic fMRI (ofMRI) allows visualization of the causal effects of specific cell types defined not only by genetic identity and cell body location, but also by axonal projection target. Finally, we show that ofMRI within the living and intact mammalian brain reveals BOLD signals in downstream targets distant from the stimulus, indicating that this approach can be used to map the global effects of controlling a local cell population. In this respect, unlike both conventional fMRI studies based on correlations14 and fMRI with electrical stimulation that will also directly drive afferent and nearby axons, this ofMRI approach provides causal information about the global circuits recruited by defined local neuronal activity patterns. Together these findings provide an empirical foundation for the widely-used fMRI BOLD signal, and the features of ofMRI define a potent tool that may be suitable for functional circuit analysis as well as global phenotyping of dysfunctional circuitry.

Self-Assembled Plasmonic Nanoparticle Clusters

(In addition to MRI and medical physics, it’s worth keeping an open mind and keeping tabs on various other branches of physics and science. To that end, I’ll highlight interesting papers or research that strikes my fancy from time to time.)

Eric Berger aka SciGuy, a science columnist at the Houston Chronicle, points to a new paper in Science that introduces new “metamaterials” which can manipulate light, which are easy to fabricate (in principle). Eric makes the analogy to this being as much a game-changer as lasers were when they were invented almost exactly 50 years ago.

Here’s the abstract of the paper:

Self-Assembled Plasmonic Nanoparticle Clusters

The self-assembly of colloids is an alternative to top-down processing that enables the fabrication of nanostructures. We show that self-assembled clusters of metal-dielectric spheres are the basis for nanophotonic structures. By tailoring the number and position of spheres in close-packed clusters, plasmon modes exhibiting strong magnetic and Fano-like resonances emerge. The use of identical spheres simplifies cluster assembly and facilitates the fabrication of highly symmetric structures. Dielectric spacers are used to tailor the interparticle spacing in these clusters to be approximately 2 nanometers. These types of chemically synthesized nanoparticle clusters can be generalized to other two- and three-dimensional structures and can serve as building blocks for new metamaterials.

and here’s a link to the full text of the article. As with lasers when they were first introduced, it’s a challenge to the imagination to envision how this might be used or applied. What possible medical imaging applications could this be exploited for? That’s the billion dollar question 🙂

MRI of acute Wiiitis

Magnetic resonance imaging of acute “wiiitis” of the upper extremity.

We present the first reported case of acute “wiiitis”, documented clinically and by imaging, of the upper extremity, caused by prolonged participation in a physically interactive virtual video-game. Unenhanced magnetic resonance imaging (MRI) demonstrated marked T2-weighted signal abnormality within several muscles of the shoulder and upper arm, without evidence of macroscopic partial- or full-thickness tearing of the muscle or of intramuscular hematoma.

Nett MP, Collins MS, Sperling JW. Skeletal Radiol. 2008 May;37(5):481-3. PMID 18259743.

It was really just a matter of time… the floodgates are now open. I expect that the musculoskeletal specialists are eagerly anticipating the release of the Wii Fit

NSFW MRI: Sex at 1.5T

That’s “not safe for work”, not “national science foundation” up there in the acronym. It was surely inevitable that this amazing, subtle and elegant technology would eventually be applied to more scatological pursuits. The following paper is a classic in this genre.

Magnetic resonance imaging of male and female genitals during coitus and female sexual arousal.

OBJECTIVE: To find out whether taking images of the male and female genitals during coitus is feasible and to find out whether former and current ideas about the anatomy during sexual intercourse and during female sexual arousal are based on assumptions or on facts. DESIGN: Observational study. SETTING: University hospital in the Netherlands. METHODS: Magnetic resonance imaging was used to study the female sexual response and the male and female genitals during coitus. Thirteen experiments were performed with eight couples and three single women. RESULTS: The images obtained showed that during intercourse in the “missionary position” the penis has the shape of a boomerang and 1/3 of its length consists of the root of the penis. During female sexual arousal without intercourse the uterus was raised and the anterior vaginal wall lengthened. The size of the uterus did not increase during sexual arousal. CONCLUSION: Taking magnetic resonance images of the male and female genitals during coitus is feasible and contributes to understanding of anatomy.

Schultz et al, BMJ. 1999 Dec 18-25;319(7225):1596-600. PMID 10600954.

Continue reading “NSFW MRI: Sex at 1.5T”

short-axis PROPELLER

One of the more interesting abstracts from last year’s ISMRM in Seattle has now been published as a full manuscript:

Propeller EPI in the other direction

A new propeller EPI pulse sequence with reduced sensitivity to field inhomogeneities is proposed. Image artifacts such as blurring due to Nyquist ghosting and susceptibility gradients are investigated and compared with those obtained in previous propeller EPI studies. The proposed propeller EPI sequence uses a readout that is played out along the short axis of the propeller blade, orthogonal to the readout used in previous propeller methods. In contrast to long-axis readout propeller EPI, this causes the echo spacing between two consecutive phase-encoding (PE) lines to decrease, which in turn increases the k-space velocity in this direction and hence the pseudo-bandwidth. Long- and short-axis propeller EPI, and standard single-shot EPI sequences were compared on phantoms and a healthy volunteer. Diffusion-weighted imaging (DWI) was also performed on the volunteer. Short-axis propeller EPI produced considerably fewer image artifacts compared to the other two sequences. Further, the oblique blades for the long-axis propeller EPI were also prone to one order of magnitude higher residual ghosting than the proposed short-axis propeller EPI.

Skare S et al, Magn Reson Med. 2006 Jun;55(6):1298. PMID: 16676335

Continue reading “short-axis PROPELLER”

PROPELLER-EPI for high-resolution DTI

PROPELLER-EPI with parallel imaging using a circularly symmetric phased-array RF coil at 3.0 T: application to high-resolution diffusion tensor imaging

A technique integrating multishot periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) and parallel imaging is presented for diffusion echo-planar imaging (EPI) at high spatial resolution. The method combines the advantages of parallel imaging to achieve accelerated sampling along the phase-encoding direction, and PROPELLER acquisition to further decrease the echo train length (ETL) in EPI. With an eight-element circularly symmetric RF coil, a parallel acceleration factor of 4 was applied such that, when combined with PROPELLER acquisition, a reduction of geometric distortions by a factor substantially greater than 4 was achieved. The resulting phantom and human brain images acquired with a 256 x 256 matrix and an ETL of only 16 were visually identical in shape to those acquired using the fast spin-echo (FSE) technique, even without field-map corrections. It is concluded that parallel PROPELLER-EPI is an effective technique that can substantially reduce susceptibility-induced geometric distortions at high field strength.

Chuang TC et al. Magn Reson Med. 2006 Dec;56(6):1352-8. PMID: 17051531

Discussion below the fold…. Continue reading “PROPELLER-EPI for high-resolution DTI”

reviewing Peer Review

Ars Technica has a nice summary of a recent paper in PLoS that attempted to assess the quality of the peer review process. From the Ars summary:

To examine what makes a good reviewer, they took advantage of the journal Annals of Emergency Medicine, which has maintained a detailed database of reviewers and post-review ratings (on a five-point scale) of their work, performed by the editors of the journal. The researchers contacted the reviewers and surveyed them about various factors that might contribute to skill in the process. A diverse set of 306 reviewers who had performed a total of nearly 3,000 reviews were used as the data set.

[…]

In news that may be disturbing for journal editors everywhere, very few factors leapt out as having a consistent and significant correlation with the quality of a review, although some factors did have strong correlations in individual tests. The only positive factors linked to quality of reviews were age (younger reviewers were better) and working at an academic hospital. Ironically, service on an Institutional Review Board, which evaluates and approves experiments on humans, consistently correlated with lower-quality peer reviews. Even these factors, however, were only slightly better than random at predicting review quality.

Ultimately the peer review process is always going to have a subjective component to it, since the processes of intuition and patterning that are fundamental to scientific insight and understanding are not really very deterministic. But there’s another possible reason why the study failed to find strong correlates of review quality; the very assessment of quality itself is equally subjective. I personally believe that the peer review system is like democracy – far from ideal but better than anything else out there. The best way to ensure general quality is to ensure that a maximum number of scientists in a given field participate in the process. Perhaps one way to achieve this would be to extend reviewer privileges to graduate students who have passed oral qualifiers?

Journal article citation: Callaham ML, Tercier J (2007) The Relationship of Previous Training and Experience of Journal Peer Reviewers to Subsequent Review Quality. PLoS Med 4(1): e40 doi:10.1371/journal.pmed.0040040

Related article: Kotchen TA, Lindquist T, Miller Sostek A, Hoffmann R, Malik K, Stanfield B. Outcomes of National Institutes of Health peer review of clinical grant applications. J Investig Med. 2006 Jan;54(1):13-9. PMID: 16409886