FIRST AMENDMENT TO THE COLLABORATION, LICENSE AND SUPPLY AGREEMENT

Exhibit 10.1

FIRST AMENDMENT

to

the Collaboration, License and Supply Agreement, dated July 6, 2004

by and between

Acusphere Inc. (“Acusphere”)

and

Nycomed Danmark ApS (“Nycomed”)

This First Amendment (the “First Amendment”), effective as of October 19, 2005, is entered into by and between Acusphere and Nycomed (the “Parties”).

WHEREAS, the Parties entered into a Collaboration, License and Supply Agreement, dated July 6, 2004 (“the Agreement”); and

WHEREAS, the Parties have agreed to make a prepayment to Acusphere of a certain amount, such amount to be deducted from Nycomed’s next milestone payment under the Agreement; and

WHEREAS, the agreed prepayment amount shall be used by Acusphere to accelerate the trademark activities related to the Product (as defined in the Agreement);

NO