From Harvard Gazette (US) : “New imaging technique may boost biology and neuroscience research”

From Harvard Gazette (US)

At

Harvard University (US)

July 7, 2021
Juan Siliezar

Scientists hope it will let them see inner workings of complex systems.

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Dushan Wadduwage works with a laser in his Northwest lab where he does research on deep tissue imaging. Credit: Jon Chase/Harvard Staff Photographer.

Microscopists have long sought a way to produce high-quality, deep-tissue imaging of living subjects in a timely fashion. To date, they have had to choose between image quality or speed when looking into the inner workings of complex biological systems.

A better imaging system would have a powerful impact on researchers in biology and in neuroscience, experts say. Now Dushan N. Wadduwage, a John Harvard Distinguished Science Fellow in imaging at the FAS Center of Advanced Imaging, along with a team from MIT, has detailed a new technique that would make that possible in a report in Science Advances.

In the paper, the team presents a new process that uses computational imaging to get high-resolution images 100 to 1,000 times faster than other state-of-the-art technologies using complex algorithms and machine learning. The method can shorten a process that often takes months into a matter of days.

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TFM and DEEP-TFM images of a mouse muscle specimen at a 190-um-deep imaging plane. The blue and red channels are respectively nucleus (stained with Hoechst 33342) and F-actin (stained with Alexa Fluor 568 Phalloidin). Courtesy of Dushan N. Wadduwage.

The system called De-scattering with Excitation Patterning (or DEEP) is believed to be the first of its kind and may one day lead to new understanding of how complicated processes, such as those in the brain, function, because DEEP can capture images other microscopes cannot.

Because the new system has the potential to actually speed up what they can image along with how fast they can do it, “scientists will be able to image fast processes they haven’t been able to capture before, like what happens when a neuron fires or how the signals move around in the brain,” Wadduwage said. “Also, because it’s technically faster, you can image a larger volume of area at one time, not just a small field of view as you would with a slower imaging system. It’s like being able to look at a much larger picture, and this is very important for neuroscientists and other biologists to actually get better statistics as well as to see what’s happening around the area being imaged.”

The system works like many other animal-imaging techniques. Near-infrared laser light is used to penetrate deep through biological tissue that scatters the light. That light excites the fluorescent molecules the researchers want to image, and these emit signals that the microscope captures to form an image.

There have been two main ways these types of images are taken. Point-scanning multiphoton microscopy can penetrate deep into a specimen and capture high-quality images, but this process is extremely slow because the image is formed one point at a time. Capturing a centimeter-sized image, for example, can take months. It also limits studies of fast biological dynamics, such as neurons firing. The other method is called temporal focusing microscopy. This is much faster and can capture images at a wider scale, but it is unable to capture high-resolution images at anything deeper than a few millionths of a meter. The fluorescent light scatters too much, causing the image to degrade when the camera detects it.

DEEP, however, allows for wide-scale and quick tissue penetration, and produces high-resolution images. The system projects a wide light into the subject as in the temporal microscopy method, but that laser light is in a specific pattern. The computational-imaging algorithm that knows the initial pattern takes in the information gathered to reverse the process when it gets scattered and then reconstructs it, de-scattering the image. This is especially notable since it takes the reconstruction of structural features from millions of measurements to tens and hundreds. DEEP can image hundreds of microns deep through scattering tissue comparable to point-scanning techniques.

DEEP is still in its early years of development, but is emerging from its proof-of-concept phase.

“We showed that we can image about 300 microns into the brains of live mice,” Wadduwage said. “But since this is only the first demonstration, almost all aspects of the technique have room for improvement.”

See the full article here .

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Harvard University (US) is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s bestknown landmark.

Harvard University (US) has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

The Massachusetts colonial legislature, the General Court, authorized Harvard University (US)’s founding. In its early years, Harvard College primarily trained Congregational and Unitarian clergy, although it has never been formally affiliated with any denomination. Its curriculum and student body were gradually secularized during the 18th century, and by the 19th century, Harvard University (US) had emerged as the central cultural establishment among the Boston elite. Following the American Civil War, President Charles William Eliot’s long tenure (1869–1909) transformed the college and affiliated professional schools into a modern research university; Harvard became a founding member of the Association of American Universities in 1900. James B. Conant led the university through the Great Depression and World War II; he liberalized admissions after the war.

The university is composed of ten academic faculties plus the Radcliffe Institute for Advanced Study. Arts and Sciences offers study in a wide range of academic disciplines for undergraduates and for graduates, while the other faculties offer only graduate degrees, mostly professional. Harvard has three main campuses: the 209-acre (85 ha) Cambridge campus centered on Harvard Yard; an adjoining campus immediately across the Charles River in the Allston neighborhood of Boston; and the medical campus in Boston’s Longwood Medical Area. Harvard University (US)’s endowment is valued at $41.9 billion, making it the largest of any academic institution. Endowment income helps enable the undergraduate college to admit students regardless of financial need and provide generous financial aid with no loans The Harvard Library is the world’s largest academic library system, comprising 79 individual libraries holding about 20.4 million items.

Harvard University (US) has more alumni, faculty, and researchers who have won Nobel Prizes (161) and Fields Medals (18) than any other university in the world and more alumni who have been members of the U.S. Congress, MacArthur Fellows, Rhodes Scholars (375), and Marshall Scholars (255) than any other university in the United States. Its alumni also include eight U.S. presidents and 188 living billionaires, the most of any university. Fourteen Turing Award laureates have been Harvard affiliates. Students and alumni have also won 10 Academy Awards, 48 Pulitzer Prizes, and 108 Olympic medals (46 gold), and they have founded many notable companies.

Colonial

Harvard University (US) was established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. In 1638, it acquired British North America’s first known printing press. In 1639, it was named Harvard College after deceased clergyman John Harvard, an alumnus of the University of Cambridge(UK) who had left the school £779 and his library of some 400 volumes. The charter creating the Harvard Corporation was granted in 1650.

A 1643 publication gave the school’s purpose as “to advance learning and perpetuate it to posterity, dreading to leave an illiterate ministry to the churches when our present ministers shall lie in the dust.” It trained many Puritan ministers in its early years and offered a classic curriculum based on the English university model—many leaders in the colony had attended the University of Cambridge—but conformed to the tenets of Puritanism. Harvard University (US) has never affiliated with any particular denomination, though many of its earliest graduates went on to become clergymen in Congregational and Unitarian churches.

Increase Mather served as president from 1681 to 1701. In 1708, John Leverett became the first president who was not also a clergyman, marking a turning of the college away from Puritanism and toward intellectual independence.

19th century

In the 19th century, Enlightenment ideas of reason and free will were widespread among Congregational ministers, putting those ministers and their congregations in tension with more traditionalist, Calvinist parties. When Hollis Professor of Divinity David Tappan died in 1803 and President Joseph Willard died a year later, a struggle broke out over their replacements. Henry Ware was elected to the Hollis chair in 1805, and the liberal Samuel Webber was appointed to the presidency two years later, signaling the shift from the dominance of traditional ideas at Harvard to the dominance of liberal, Arminian ideas.

Charles William Eliot, president 1869–1909, eliminated the favored position of Christianity from the curriculum while opening it to student self-direction. Though Eliot was the crucial figure in the secularization of American higher education, he was motivated not by a desire to secularize education but by Transcendentalist Unitarian convictions influenced by William Ellery Channing and Ralph Waldo Emerson.

20th century

In the 20th century, Harvard University (US)’s reputation grew as a burgeoning endowment and prominent professors expanded the university’s scope. Rapid enrollment growth continued as new graduate schools were begun and the undergraduate college expanded. Radcliffe College, established in 1879 as the female counterpart of Harvard College, became one of the most prominent schools for women in the United States. Harvard University (US) became a founding member of the Association of American Universities in 1900.

The student body in the early decades of the century was predominantly “old-stock, high-status Protestants, especially Episcopalians, Congregationalists, and Presbyterians.” A 1923 proposal by President A. Lawrence Lowell that Jews be limited to 15% of undergraduates was rejected, but Lowell did ban blacks from freshman dormitories.

President James B. Conant reinvigorated creative scholarship to guarantee Harvard University (US)’s preeminence among research institutions. He saw higher education as a vehicle of opportunity for the talented rather than an entitlement for the wealthy, so Conant devised programs to identify, recruit, and support talented youth. In 1943, he asked the faculty to make a definitive statement about what general education ought to be, at the secondary as well as at the college level. The resulting Report, published in 1945, was one of the most influential manifestos in 20th century American education.

Between 1945 and 1960, admissions were opened up to bring in a more diverse group of students. No longer drawing mostly from select New England prep schools, the undergraduate college became accessible to striving middle class students from public schools; many more Jews and Catholics were admitted, but few blacks, Hispanics, or Asians. Throughout the rest of the 20th century, Harvard became more diverse.

Harvard University (US)’s graduate schools began admitting women in small numbers in the late 19th century. During World War II, students at Radcliffe College (which since 1879 had been paying Harvard University (US) professors to repeat their lectures for women) began attending Harvard University (US) classes alongside men. Women were first admitted to the medical school in 1945. Since 1971, Harvard University (US) has controlled essentially all aspects of undergraduate admission, instruction, and housing for Radcliffe women. In 1999, Radcliffe was formally merged into Harvard University (US).

21st century

Drew Gilpin Faust, previously the dean of the Radcliffe Institute for Advanced Study, became Harvard University (US)’s first woman president on July 1, 2007. She was succeeded by Lawrence Bacow on July 1, 2018.