Preheat oven to 375 degrees. Coat a 13x9 baking dish with cooking spray. Set aside. In large skillet, heat oil to medium heat. Add Brussels sprouts and cook 5-6 minutes, stirring only occasionally, until crispy.
Add Panko breadcrumbs and toast another minute. Stir in salt. Set aside. Bring a large pot of water to a boil. Cook pasta according to package directions. Drain and set aside.
In the same pot, heat butter to medium high heat. Whisk in flour and cook, whisking continuously, for 1-2 minutes. Slowly add milk, whisking vigorously until incorporated and smooth. Let simmer 3-4 minutes, whisking frequently, until thickened.
Whisk in salt, pepper, cayenne and dry mustard. Remove from heat and whisk in cheeses until melted. Taste and adjust seasoning, if necessary. Add cooked pasta and stir until combined.
Transfer mac and cheese to the prepared baking dish. Evenly top with crispy Brussels sprouts mixture. Bake 15-20 minutes, until cheese is bubbly and topping is slightly browned.