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Feb 1 2024 Brigham and Women's Hospital

Brigham and MIT researchers uncovered never-before-seen details in human brain tissue with new, inexpensive microscopy technology.

Key takeaways: Researchers have developed a new microscopy technology called decrowding expansion pathology (dExPath) to analyze brain tissue. By pulling proteins apart with dExPath, researchers can stain proteins in tissue that could not be accessed before, highlighting nanometer sized structures or even cell populations that were previously hidden. This "super-resolution imaging" technology has the potential to provide insights that could improve diagnostic strategies and patient outcomes.

Researchers from Brigham and Women's Hospital, a founding member of Mass General Brigham, and the Massachusetts Institute of Technology (MIT) have unveiled unprecedentedly detailed images of brain cancer tissue through the use of a new microscopy technology called decrowding expansion pathology (dExPath).Their findings, published in Science Translational Medicine, provide novel insights into brain cancer development, with potential implications for advancing the diagnosis and treatment of aggressive neurological diseases.

"In the past, we have relied on expensive, super-resolution microscopes that only very well-funded labs could afford, required specialized training to use, and are often impractical for high-throughput analyses of brain tissues at the molecular level," said Pablo Valdes, MD, PhD, a neurosurgery resident alumnus at the Brigham and lead author of the study. "This technology brings reliable, super-resolution imaging to the clinic, enabling scientists to study neurological diseases at a never-before-achieved nanoscale level on conventional clinical samples with conventional microscopes."

Researchers previously relied on costly, super-high-resolution microscopes to image nanoscale structures in cells and brain tissue, and, even with the most advanced technology, they often struggled to effectively capture these structures at the nanoscale level.

Ed Boyden, PhD, the Y. Eva Tan Professor in Neurotechnology at MIT and co-senior author on this study, began addressing this problem by labeling tissues, and then chemically modifying them to enable uniform physical expansion of tissues. However, this expansion technology was far from perfect. Relying on enzymes known as proteases to break up tissue, scientists found that this chemical treatment with enzymes destroyed proteins before they could analyze them, leaving behind only a skeleton of the original structure, retaining only the labels.

Working together, Boyden and E. Antonio Chiocca, MD, PhD, Neurosurgery Chair at Brigham and Women's Hospital and co-senior author on this study, mentored Valdes during his training as a neurosurgeon-scientist, to develop novel chemistries with dExPath to address the limitations of the original expansion technology.

Their new technology chemically modifies tissues by embedding them in a gel and 'softening' the tissues with a special chemical treatment that separates protein structures without destroying them and which allows tissues to expand. This provided exciting findings to the MIT and Brigham researchers, who routinely use commercially available antibodies to bind to and illuminate biomarkers in a sample. Antibodies, however, are large and many times cannot easily penetrate cell structures to reach their target. Now, by pulling proteins apart with dExPath, these same antibodies used for staining can penetrate spaces to bind proteins in tissue that could not be accessed before expansion, highlighting nanometer sized structures or even cell populations that were previously hidden. The human brain has several stop guards in place to protect itself from pathogens and environmental toxins. But these elements make studying brain activity challenging. It can be a bit like driving a car through mud and ditches. We cannot access certain cell structures in the brain because of barriers that stand in the way. That is just is one of the reasons that this new technology could be so practice changing. If we can take more detailed and accurate images of brain tissue, we can identify more biomarkers and be better equipped to diagnose and treat aggressive brain diseases."

E. Antonio Chiocca, MD, PhD, Chair of the Department of Neurosurgery, Brigham and Women's Hospital Related StoriesScientists reveal direct link between mitochondrial DNA mutations and cancer treatment responseSignificant link found between recent weight loss and increased cancer riskNHS health checks linked to reduced risk of heart, brain, kidney, and liver diseases

To validate the effectiveness of dExPath, Boyden and Chiocca's team applied the technology to healthy human brain tissue, high and low-grade brain cancer tissues, and brain tissues affected by neurodegenerative diseases including Alzheimer's and Parkinson's diseases. Investigators stained tissue for brain and disease specific biomarkers and captured images before and after expanding samples with dExPath.

The results revealed uniform and consistent expansion of the tissue without distortion, enabling accurate analysis of protein structures. Additionally, dExPath effectively eliminated fluorescent signals in brain tissue called lipofuscin, which makes imaging of subcellular structures in brain tissues very difficult, further enhancing image quality. Further, dExPath provided stronger fluorescent signals for improved labeling as well as simultaneous labeling of up to 16 biomarkers in the same tissue specimen. Notably, dExPath imaging revealed that tumors previously classified as "low-grade" contained more aggressive features and cell populations, suggesting the tumor could become far more dangerous than anticipated.

While promising, dExPath requires validation on larger sample sizes before it can contribute to the diagnosis of neurological conditions such as brain cancer. Valdes underscores that, although still in its early stages, his team aspires for this technology to eventually serve as a diagnostic tool, ultimately enhancing patient outcomes.

"We hope that with this technology, we can better understand at the nanoscale levels the intricate workings of brain tumors and their interactions with the nervous system without depending on exorbitantly expensive lab equipment," said Valdes who is now an assistant professor of neurosurgery and Jennie Sealy Distinguished Chair in Neuroscience at the University of Texas Medical Branch. "The accessibility of dExPath will bring enable super-resolution imaging to understand biological processing at the nanometer level in human tissue in neuro-oncology and in neurological disease such as Alzheimer's and Parkinson's, and one day, could even improve diagnostic strategies and patient outcomes." Source:

Brigham and Women's HospitalJournal reference:

Valdes, P. A., et al. (2024) Improved immunostaining of nanostructures and cells in human brain specimens through expansion-mediated protein decrowding. Science Translational Medicine. doi.org/10.1126/scitranslmed.abo0049.

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Sources: Kings expected to name Holland next GM

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Sources: Kings expected to name Holland next GM

Ken Holland, who won four Stanley Cups as an executive with the Detroit Red Wings, is expected to become the next general manager of the Los Angeles Kings, multiple NHL sources told ESPN on Monday, confirming a report.

Inducted into the Hockey Hall of Fame as a builder in 2020, Holland replaces Rob Blake, the Kings’ general manager and vice president of hockey operations whose contract was not renewed after a fourth straight first-round playoff exit.

An announcement is expected later this week. Rod Pedersen, host of “The Rod Pedersen Show,” first reported the news.

Holland, 69, was the executive vice president and general manager of the Red Wings from 1997 through 2019, winning four Stanley Cups for the franchise. He was bumped upstairs in 2019 to senior vice president, clearing the way for Steve Yzerman to become the team’s general manager.

That promotion lasted only a month, as Holland left to take over the Edmonton Oilers as general manager and president of hockey operations. Powered by stars Connor McDavid and Leon Draisaitl, the team made the conference finals in 2022 and 2024, losing in Game 7 of the Stanley Cup Final last year with a roster Holland constructed. Among his key acquisitions were forward Zach Hyman (free agent) and defensemen Mattias Ekholm (via trade with Nashville) and Philip Broberg (drafted eighth in 2019). The Oilers made the playoffs in all five seasons of Holland’s tenure.

Holland’s five-year contract with the Oilers expired on July 1, 2024. Edmonton eventually hired former Blackhawks GM Stan Bowman to replace him. Since then, Holland had been working as a consultant to the NHL’s hockey operations department.

Sources told ESPN that Holland had been considering a front office role with the New York Islanders, either as team president, general manager or both. Former Montreal Canadiens GM Marc Bergevin, a senior adviser for the Kings who many believed might be their next general manager, is in the mix for the Islanders’ openings.

Kings president Luc Robitaille played for Holland’s Red Wings from 2001-2003, winning his only Stanley Cup as a player in 2002. He will now reconnect with Holland, who will take over a Kings roster that features holdovers from their Stanley Cup wins in 2012 and 2014 (Anze Kopitar and Drew Doughty), scorers in their prime (Adrian Kempe and Kevin Fiala), young players on the rise (Quinton Byfield and Brandt Clarke) and goalie Darcy Kuemper, who was a finalist for the Vezina Trophy this season.

But Los Angeles has failed to advance past the first round of the playoffs since 2014. The Kings have lost four straight first-round series to the Oilers — conveniently, Holland’s former team — including their six-game defeat this postseason.

Holland will now determine the fate of Jim Hiller, who finished his first season as Kings head coach after serving on an interim basis in 2023-24. Hiller was an assistant coach with the Red Wings for one season (2014-15) during Holland’s time in Detroit.

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Canes use ‘huge’ late goals to push Caps to brink

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Canes use 'huge' late goals to push Caps to brink

RALEIGH, N..C. — The Carolina Hurricanes twice found their two-goal margin halved in the third period of their latest playoff game with the Washington Capitals.

Each time they found a prompt response.

And that pushed the Hurricanes to within a win of the Eastern Conference finals for the second time in three seasons.

Taylor Hall scored on a breakaway chance roughly three minutes after the Washington Capitals scored their first goal, then Sean Walker added one minutes after NHL all-time goals leader Alex Ovechkin struck with a 5-on-3 one-timer. Those kept the Hurricanes in control on the way to a 5-2 win Monday night, securing a 3-1 lead in the best-of-seven second-round series.

“We get an individual effort, and that’s really what those were, good plays,” Carolina coach Rod Brind’Amour said. “But burying it, finishing your chances at a crucial time in the game. … Both of those goals were huge for us.”

Both Hall and Walker finished with two points, with Walker getting the second assist on Hall’s score and Hall returning the favor by springing Walker’s surge up the ice on the way to his first career postseason goal. But the timing of the goals stood out, with each blunting the momentum of a Washington team that had been shutout for five straight periods going back to Saturday’s 4-0 loss in Game 3.

Carolina carried a 2-0 lead into the third before Jakob Chychrun beat Frederik Andersen on a feed from Matt Roy after Roy had denied Carolina’s chance to clear the zone. That score came at the 5:18 mark of the third to add a jolt of tension rippling through the Lenovo Center after Carolina had kept a firm grip on the game to that point.

But Hall — acquired in January in the blockbuster deal that brought in Mikko Rantanen as the headliner — made a veteran read to blunt that momentum.

After being knocked to the ice in the offensive zone, Hall was getting up as the Capitals pushed the puck toward the other end. But as Hall got to center ice, he was alone — Washington coach Spencer Carbery said the defense lost track of Hall behind the forecheck and were too deep in the zone — and the Hurricanes were on the verge of collecting the puck as it went around the end wall.

So Hall turned in back toward the blue line, straddling it long enough to stay onside until Jack Roslovic‘s long pass arrived to spring the breakaway chance.

“Yeah, everyone’s asking me if I was cheating for offense,” Hall said, adding; “I thought it was just something to try.”

Hall skated in and beat Logan Thompson to the glove side at the 8:24 mark, pushing the margin back to 3-1.

“It’s a read, we had possession of the puck,” Brind’Amour said. “So that’s actually a good play by him.”

The Capitals again kept the pressure on with Ovechkin’s blast past Andersen on a two-man advantage at the 12:14 mark, dampening the rowdy zeal in Carolina’s home arena. But that’s when Hall and Walker teamed up for the goal that would reassert control.

It started on a puck battle and the unusual sight of Washington’s Rasmus Sandin skating in to get the puck from Walker, only to get the blade of his stick stuck in a gap along the boards. Walker got to his feet as Hall collected the puck, then flipped a pass to Walker as he charged up the left side.

Walker hesitated to cut inside Roslovic toward the slot and beat Thompson at the 16:45 mark, pushing the lead back to 4-2 in what became a backbreaking score.

“I feel like they were backchecking really hard, so I kind of just read that,” Walker said. “Tried to be patient. Once I stepped inside, I felt like I had a good lane so I shot it, and just happy it went in.”

Ovechkin’s blast got the NHL’s career goals leader on the scoresheet for the first time this series. Thompson finished with 32 saves.

“We’re giving ourselves some opportunities, we’re just not executing, making the play, whatever you want to call it,” Washington coach Spencer Carbery said. “And making some mistakes — and they’re capitalizing.”

To that point, the Eastern Conference’s top seed got a quick start after a Game 3 shutout, starting with Connor McMichael getting a 1-on-1 chance on Andersen in the opening minute. Aliaksei Protas followed by ringing the right post shortly after.

Washington also managed only one shot on goal during a 4-minute power play, the first 3½ minutes of those coming to close the first period.

“Their penalty kill is excellent, best in the league, has been for the last, whatever, five years call it,” Carbery said. “But it can’t look like that. It cannot look like that.”

Andrei Svechnikov added the empty-net clincher less than a minute later to deny Washington’s bid to retake home-ice advantage, the capper to Carolina’s steady response amid growing third-period danger.

“I think that’s something that’s really important, especially this time of year,” Walker said. “You’ve got to answer when teams are making their push.”

Information from The Associated Press was used in this report.

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Report: Oilers’ Pickard likely out rest of series

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Report: Oilers' Pickard likely out rest of series

Edmonton Oilers goaltender Calvin Pickard is expected to miss the remainder of the Western Conference semifinal series against the Vegas Golden Knights due to an injury, according to a TSN report on Monday.

Later Monday, with veteran Stuart Skinner in net, the Oilers defeated the Golden Knights, 3-0, in Game 4, securing a 3-1 series lead. Skinner made 23 saves in the victory.

Pickard has won all six starts in the net for the Oilers during this postseason run. After Edmonton lost the first two games against the Los Angeles Kings in the first round, coach Kris Knoblauch replaced Skinner, the team’s regular-season starter, with Pickard. The 33-year-old career backup posted wins in the next four games to help the Oilers oust the Kings and then earned victories in the first two games of the second round in Las Vegas.

Golden Knights forward Tomas Hertl fell into Pickard’s left leg during the Oilers’ 5-4 overtime triumph on May 8. The Moncton, New Brunswick, native finished the game but has not practiced since. With Skinner back in the net, host Edmonton lost 4-3 in Game 3, as Vegas forward Reilly Smith scored with 0.4 seconds remaining.

TSN reported “it will probably be at least a week” before Pickard could return, and during Game 4 on Monday night, Olivier Rodrigue was the backup netminder on the bench. Rodrigue, 24, played in just two games for Edmonton in his first NHL season.

Prior to Monday’s shutout, Skinner, who starred during the Oilers’ run to the Stanley Cup Final last spring, had allowed 15 goals in just 168 minutes of playing time this postseason and owns a lowly save percentage of .817. During the regular season, Skinner went 26-18-4, with a 2.81 goals-against average and an .896 save percentage.

Since falling down 2-0 to the Kings, the Oilers have won seven of eight postseason games. Game 5 is back in Las Vegas on Wednesday night.

Information from Field Level Media was used in this report.

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